Variant 5-140367882-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031467.3(SLC4A9):c.2338A>C(p.Asn780His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SLC4A9
NM_031467.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

SLC4A9 (HGNC:11035): (solute carrier family 4 member 9) The protein encoded by this gene is a membrane protein involved in anion exchange. Expression of this gene is mostly limited to the kidney. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

SLC4A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116714746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A9	NM_031467.3 linkuse as main transcript	c.2338A>C	p.Asn780His	missense_variant	16/22	ENST00000506757.7	NP_113655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A9	ENST00000506757.7 linkuse as main transcript	c.2338A>C	p.Asn780His	missense_variant	16/22	1	NM_031467.3	ENSP00000424424	P1	Q96Q91-3
SLC4A9	ENST00000507527.1 linkuse as main transcript	c.2410A>C	p.Asn804His	missense_variant	16/22	1		ENSP00000427661		Q96Q91-1
SLC4A9	ENST00000432095.6 linkuse as main transcript	c.2296A>C	p.Asn766His	missense_variant	16/22	1		ENSP00000410056		Q96Q91-2
SLC4A9	ENST00000506545.5 linkuse as main transcript	c.2149A>C	p.Asn717His	missense_variant	15/21	1		ENSP00000422855		Q96Q91-4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000483

AC:

AN:

248552

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

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:

0.0000540

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000331

AC:

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 06, 2022

The c.2338A>C (p.N780H) alteration is located in exon 16 (coding exon 16) of the SLC4A9 gene. This alteration results from a A to C substitution at nucleotide position 2338, causing the asparagine (N) at amino acid position 780 to be replaced by a histidine (H). 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

0.057

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.8

DANN

Benign

0.87

DEOGEN2

Benign

0.21

.;.;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.054

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

-0.090

.;.;.;N

MutationTaster

Benign

0.94

N;N;N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.92

N;N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.032

D;D;D;D

Sift4G

Uncertain

0.047

D;D;D;D

Polyphen

0.0

B;.;B;B

Vest4

0.33

MutPred

0.45

.;.;.;Gain of sheet (P = 0.0827);

MVP

0.65

ClinPred

0.065

GERP RS

4.1

Varity_R

0.083

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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