Variant 7-123129384-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022444.4(SLC13A1):c.1030A>T(p.Arg344Trp) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC13A1
NM_022444.4 missense, splice_region

Scores

Splicing: ADA: 0.9942

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A1	NM_022444.4 linkuse as main transcript	c.1030A>T	p.Arg344Trp	missense_variant, splice_region_variant	9/15	ENST00000194130.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC13A1	ENST00000194130.7 linkuse as main transcript	c.1030A>T	p.Arg344Trp	missense_variant, splice_region_variant	9/15	1	NM_022444.4	P1
SLC13A1	ENST00000439260.5 linkuse as main transcript	c.*1408A>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	12/18	1
SLC13A1	ENST00000539873.1 linkuse as main transcript	c.*697A>T		splice_region_variant, 3_prime_UTR_variant	10/16	5
SLC13A1	ENST00000427975.5 linkuse as main transcript	c.*973A>T		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	10/16	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.10e-7

AC:

AN:

1407540

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698798

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:

9.26e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 01, 2022

The c.1030A>T (p.R344W) alteration is located in exon 9 (coding exon 9) of the SLC13A1 gene. This alteration results from a A to T substitution at nucleotide position 1030, causing the arginine (R) at amino acid position 344 to be replaced by a tryptophan (W). 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

0.17

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.33

MutPred

0.66

Gain of methylation at K339 (P = 0.0449);

MVP

0.62

MPC

0.43

ClinPred

0.99

GERP RS

5.7

Varity_R

0.64

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over