7-123147252-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022444.4(SLC13A1):c.719C>T(p.Thr240Met) variant causes a missense change. The variant allele was found at a frequency of 0.00121 in 1,613,606 control chromosomes in the GnomAD database, including 26 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 0.0062 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 16 hom. )

Consequence

SLC13A1
NM_022444.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.56

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004463434).

BP6

Variant 7-123147252-G-A is Benign according to our data. Variant chr7-123147252-G-A is described in ClinVar as [Benign]. Clinvar id is 768197.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00622 (947/152242) while in subpopulation AFR AF= 0.022 (912/41542). AF 95% confidence interval is 0.0208. There are 10 homozygotes in gnomad4. There are 424 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A1	NM_022444.4 linkuse as main transcript	c.719C>T	p.Thr240Met	missense_variant	7/15	ENST00000194130.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC13A1	ENST00000194130.7 linkuse as main transcript	c.719C>T	p.Thr240Met	missense_variant	7/15	1	NM_022444.4	P1
SLC13A1	ENST00000439260.5 linkuse as main transcript	c.*1097C>T		3_prime_UTR_variant, NMD_transcript_variant	10/18	1
SLC13A1	ENST00000539873.1 linkuse as main transcript	c.*386C>T		3_prime_UTR_variant	8/16	5
SLC13A1	ENST00000427975.5 linkuse as main transcript	c.*662C>T		3_prime_UTR_variant, NMD_transcript_variant	8/16	5

Frequencies

GnomAD3 genomes

AF:

0.00621

AC:

944

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

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:

0.0000147

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00162

AC:

406

AN:

250580

Hom.:

AF XY:

0.00135

AC XY:

183

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.000841

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000683

AC:

998

AN:

1461364

Hom.:

Cov.:

AF XY:

0.000596

AC XY:

433

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.000873

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00622

AC:

947

AN:

152242

Hom.:

Cov.:

AF XY:

0.00570

AC XY:

424

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00748

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00194

AC:

236

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Benign

0.052

DEOGEN2

Benign

0.025

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.9

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.45

PROVEAN

Benign

4.2

REVEL

Benign

0.12

Sift

Benign

0.83

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.12

MVP

0.49

MPC

0.082

ClinPred

0.012

GERP RS

5.0

Varity_R

0.051

gMVP

0.43

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