Variant 7-123129431-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022444.4(SLC13A1):c.983C>T(p.Ala328Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,608,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SLC13A1
NM_022444.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Variant links:

Genes affected

SLC13A1 (HGNC:10916): (solute carrier family 13 member 1) The protein encoded by this gene is an apical membrane Na(+)-sulfate cotransporter involved in sulfate homeostasis in the kidney. Defects in this gene lead to many pathophysiologic problems. [provided by RefSeq, May 2016]

SLC13A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30039763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A1	NM_022444.4 linkuse as main transcript	c.983C>T	p.Ala328Val	missense_variant	9/15	ENST00000194130.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC13A1	ENST00000194130.7 linkuse as main transcript	c.983C>T	p.Ala328Val	missense_variant	9/15	1	NM_022444.4	P1
SLC13A1	ENST00000439260.5 linkuse as main transcript	c.*1361C>T		3_prime_UTR_variant, NMD_transcript_variant	12/18	1
SLC13A1	ENST00000539873.1 linkuse as main transcript	c.*650C>T		3_prime_UTR_variant	10/16	5
SLC13A1	ENST00000427975.5 linkuse as main transcript	c.*926C>T		3_prime_UTR_variant, NMD_transcript_variant	10/16	5

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248388

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134340

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1457608

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725142

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:

0.0000252

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150692

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73530

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.983C>T (p.A328V) alteration is located in exon 9 (coding exon 9) of the SLC13A1 gene. This alteration results from a C to T substitution at nucleotide position 983, causing the alanine (A) at amino acid position 328 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.79

M_CAP

Benign

0.012

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.1

REVEL

Benign

0.15

Sift

Benign

0.10

Sift4G

Benign

0.14

Polyphen

0.92

Vest4

0.33

MutPred

0.54

Gain of methylation at K327 (P = 0.0354);

MVP

0.31

MPC

0.21

ClinPred

0.85

GERP RS

4.8

Varity_R

0.23

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

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