Variant 5-177393763-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5

The NM_003052.5(SLC34A1):c.1006T>G(p.Cys336Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC34A1
NM_003052.5 missense, splice_region

Scores

Splicing: ADA: 0.03160

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.12

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM1

In a disulfide_bond (size 297) in uniprot entity NPT2A_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_003052.5

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.928

PP5

Variant 5-177393763-T-G is Pathogenic according to our data. Variant chr5-177393763-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 234929.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-177393763-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC34A1	NM_003052.5 linkuse as main transcript	c.1006T>G	p.Cys336Gly	missense_variant, splice_region_variant	9/13	ENST00000324417.6	NP_003043.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A1	ENST00000324417.6 linkuse as main transcript	c.1006T>G	p.Cys336Gly	missense_variant, splice_region_variant	9/13	1	NM_003052.5	ENSP00000321424	P1	Q06495-1
SLC34A1	ENST00000507685.5 linkuse as main transcript	n.1297T>G		splice_region_variant, non_coding_transcript_exon_variant	7/10	2
SLC34A1	ENST00000513614.1 linkuse as main transcript	n.908T>G		splice_region_variant, non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hypercalcemia, infantile, 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Pathogenic

0.82

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.64

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-9.9

REVEL

Uncertain

0.30

Sift

Benign

0.047

Sift4G

Benign

0.10

Polyphen

0.24

Vest4

0.86

MutPred

0.73

Gain of disorder (P = 0.01);

MVP

0.38

MPC

0.088

ClinPred

0.99

GERP RS

5.5

Varity_R

0.86

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.032

dbscSNV1_RF

Benign

0.15

SpliceAI score (max)

0.030

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