5-177385766-G-T

Position:

chr5-177385766-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_003052.5(SLC34A1):c.25G>T(p.Gly9Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,612,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC34A1
NM_003052.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 1.36

Variant links:

Genes affected

SLC34A1 (HGNC:11019): (solute carrier family 34 member 1) Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; phosphate ion transport; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC34A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09033567).

BP6

Variant 5-177385766-G-T is Benign according to our data. Variant chr5-177385766-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 352953.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC34A1	NM_003052.5 linkuse as main transcript	c.25G>T	p.Gly9Trp	missense_variant	2/13	ENST00000324417.6
SLC34A1	NM_001167579.2 linkuse as main transcript	c.25G>T	p.Gly9Trp	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC34A1	ENST00000324417.6 linkuse as main transcript	c.25G>T	p.Gly9Trp	missense_variant	2/13	1	NM_003052.5	P1	Q06495-1
SLC34A1	ENST00000512593.5 linkuse as main transcript	c.25G>T	p.Gly9Trp	missense_variant	2/9	2			Q06495-2
SLC34A1	ENST00000504577.5 linkuse as main transcript	c.25G>T	p.Gly9Trp	missense_variant	2/4	4
SLC34A1	ENST00000507685.5 linkuse as main transcript	n.109G>T		non_coding_transcript_exon_variant	2/10	2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000487

AC:

AN:

246316

Hom.:

AF XY:

0.0000450

AC XY:

AN XY:

133260

show subpopulations

Gnomad AFR exome

AF:

0.000567

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460830

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000118

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.25G>T (p.G9W) alteration is located in exon 2 (coding exon 1) of the SLC34A1 gene. This alteration results from a G to T substitution at nucleotide position 25, causing the glycine (G) at amino acid position 9 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 08, 2022

This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 9 of the SLC34A1 protein (p.Gly9Trp). This variant is present in population databases (rs148669433, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with SLC34A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 352953). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Hypophosphatemic nephrolithiasis/osteoporosis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.29

.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.090

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.9

D;N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.95

.;.;P

Vest4

0.46, 0.45

MVP

0.59

MPC

0.26

ClinPred

0.15

GERP RS

1.7

Varity_R

0.10

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over