dbSNP rs140504210: SLC9A1:p.Asp759Tyr (chr1-27100480-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003047.5(SLC9A1):c.2275G>T(p.Asp759Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D759N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC9A1
NM_003047.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

Genes affected

SLC9A1 (HGNC:11071): (solute carrier family 9 member A1) This gene encodes a Na+/H+ antiporter that is a member of the solute carrier family 9. The encoded protein is a plasma membrane transporter that is expressed in the kidney and intestine. This protein plays a central role in regulating pH homeostasis, cell migration and cell volume. This protein may also be involved in tumor growth. [provided by RefSeq, Sep 2011]

SLC9A1 Gene-Disease associations (from GenCC):

Lichtenstein-Knorr syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia

SLC9A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31379718).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003047.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9A1	NM_003047.5	MANE Select	c.2275G>T	p.Asp759Tyr	missense	Exon 12 of 12	NP_003038.2
	SLC9A1	NR_046474.2		n.2605G>T		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9A1	ENST00000263980.8	TSL:1 MANE Select	c.2275G>T	p.Asp759Tyr	missense	Exon 12 of 12	ENSP00000263980.3	P19634-1
SLC9A1	ENST00000854572.1		c.2275G>T	p.Asp759Tyr	missense	Exon 13 of 13	ENSP00000524631.1
SLC9A1	ENST00000854573.1		c.2110G>T	p.Asp704Tyr	missense	Exon 12 of 12	ENSP00000524632.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

M_CAP

Benign

0.084

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PhyloP100

1.1

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

REVEL

Benign

0.18

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.036

Polyphen

0.99

Vest4

0.38

MutPred

0.29

Gain of phosphorylation at D759 (P = 5e-04)

MVP

0.17

MPC

0.91

ClinPred

0.75

GERP RS

4.2

Varity_R

0.11

gMVP

0.51

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over