Variant 4-25662726-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006424.3(SLC34A2):c.134T>C(p.Val45Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,614,120 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.014 ( 45 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 43 hom. )

Consequence

SLC34A2
NM_006424.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.840

Variant links:

Genes affected

SLC34A2 (HGNC:11020): (solute carrier family 34 member 2) The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC34A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002961576).

BP6

Variant 4-25662726-T-C is Benign according to our data. Variant chr4-25662726-T-C is described in ClinVar as [Benign]. Clinvar id is 780909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2083/152234) while in subpopulation AFR AF= 0.0475 (1975/41536). AF 95% confidence interval is 0.0458. There are 45 homozygotes in gnomad4. There are 977 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC34A2	NM_006424.3 linkuse as main transcript	c.134T>C	p.Val45Ala	missense_variant	3/13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2 linkuse as main transcript	c.131T>C	p.Val44Ala	missense_variant	3/13		NP_001171469.2
SLC34A2	NM_001177999.2 linkuse as main transcript	c.131T>C	p.Val44Ala	missense_variant	3/13		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8 linkuse as main transcript	c.134T>C	p.Val45Ala	missense_variant	3/13	1	NM_006424.3	ENSP00000371483	P4	O95436-1

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2066

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00329

AC:

827

AN:

251468

Hom.:

AF XY:

0.00220

AC XY:

299

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0451

Gnomad AMR exome

AF:

0.00199

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:

0.000141

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00136

AC:

1988

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

865

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0485

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.0137

AC:

2083

AN:

152234

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

977

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0475

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.0153

ESP6500AA

AF:

0.0443

AC:

195

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00418

AC:

508

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.10

DANN

Benign

0.36

DEOGEN2

Benign

0.044

.;.;.;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.46

.;T;.;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;.;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

.;N;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.63

.;T;T;T;T;T

Sift4G

Benign

0.61

.;T;T;T;T;T

Polyphen

0.0030

B;.;B;B;B;.

Vest4

0.14, 0.13, 0.13

MVP

0.43

MPC

0.29

ClinPred

0.010

GERP RS

3.0

Varity_R

0.037

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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