Variant X-46607134-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001257291.2(SLC9A7):c.1999G>A(p.Gly667Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,209,195 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Consequence

SLC9A7
NM_001257291.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

SLC9A7 (HGNC:17123): (solute carrier family 9 member A7) This gene encodes a sodium and potassium/ proton antiporter that is a member of the solute carrier family 9 protein family. The encoded protein is primarily localized to the trans-Golgi network and is involved in maintaining pH homeostasis in organelles along the secretory and endocytic pathways. This protein may enhance cell growth of certain breast tumors. This gene is part of a gene cluster on chromosome Xp11.23. A pseudogene of this gene is found on chromosome 12. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

SLC9A7 links:

SLC9A7 (HGNC:):

SLC9A7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A7	NM_001257291.2 linkuse as main transcript	c.1999G>A	p.Gly667Arg	missense_variant	17/17	ENST00000616978.5	NP_001244220.1	A0A087WXD1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A7	ENST00000616978.5 linkuse as main transcript	c.1999G>A	p.Gly667Arg	missense_variant	17/17	1	NM_001257291.2	ENSP00000480916.1		A0A087WXD1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111390

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33572

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:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

182127

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66667

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000726

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1097805

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363163

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:

0.0000494

Gnomad4 NFE exome

AF:

0.0000226

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111390

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33572

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:

0.0000377

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual developmental disorder, X-linked 108

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Nov 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.072

T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Pathogenic

0.64

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-2.4

.;N

REVEL

Benign

0.25

Sift

Benign

0.072

.;T

Sift4G

Benign

0.12

T;T

Polyphen

1.0

.;D

Vest4

0.65

MutPred

0.21

.;Loss of sheet (P = 0.0181);

MVP

0.57

MPC

1.7

ClinPred

0.58

GERP RS

5.1

Varity_R

0.54

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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