Genetic Variant NM_004594.3:c.10G>C (chr16-67249024-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004594.3(SLC9A5):c.10G>C(p.Ala4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. A4S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC9A5
NM_004594.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.251

Publications

0 publications found

Variant links:

Genes affected

SLC9A5 (HGNC:11078): (solute carrier family 9 member A5) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Implicated in end stage renal disease. [provided by Alliance of Genome Resources, Apr 2022]

SLC9A5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24420846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004594.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9A5	NM_004594.3	MANE Select	c.10G>C	p.Ala4Pro	missense	Exon 1 of 16	NP_004585.1	Q14940
SLC9A5	NM_001323973.2		c.10G>C	p.Ala4Pro	missense	Exon 1 of 16	NP_001310902.1
SLC9A5	NM_001323972.2		c.10G>C	p.Ala4Pro	missense	Exon 1 of 15	NP_001310901.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC9A5	ENST00000299798.16	TSL:1 MANE Select	c.10G>C	p.Ala4Pro	missense	Exon 1 of 16	ENSP00000299798.11	Q14940
SLC9A5	ENST00000563723.5	TSL:1	n.48G>C		non_coding_transcript_exon	Exon 1 of 15
SLC9A5	ENST00000564812.5	TSL:1	n.10G>C		non_coding_transcript_exon	Exon 1 of 15	ENSP00000455058.1	H3BNY2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1273888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

626984

African (AFR)

AF:

0.00

AC:

AN:

25920

American (AMR)

AF:

0.00

AC:

AN:

22218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21592

East Asian (EAS)

AF:

0.00

AC:

AN:

27980

South Asian (SAS)

AF:

0.00

AC:

AN:

67584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3670

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1022080

Other (OTH)

AF:

0.00

AC:

AN:

51692

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

PhyloP100

-0.25

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.56

REVEL

Benign

0.089

Sift

Benign

0.046

Sift4G

Benign

0.14

Polyphen

0.84

Vest4

0.19

MutPred

0.16

Loss of MoRF binding (P = 0.0232)

MVP

0.74

MPC

0.76

ClinPred

0.16

GERP RS

2.9

PromoterAI

0.16

Neutral

(source)

Varity_R

0.20

gMVP

0.71

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

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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