5-140367462-G-C

Position:

• chr5-140367462-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031467.3(SLC4A9):​c.2056G>C​(p.Ala686Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A9 NM_031467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0870

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]

ACMG classification

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=0.22620839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A9	NM_031467.3	c.2056G>C	p.Ala686Pro	missense_variant	15/22	ENST00000506757.7	NP_113655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A9	ENST00000506757.7	c.2056G>C	p.Ala686Pro	missense_variant	15/22	1	NM_031467.3	ENSP00000424424	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.2056G>C (p.A686P) alteration is located in exon 15 (coding exon 15) of the SLC4A9 gene. This alteration results from a G to C substitution at nucleotide position 2056, causing the alanine (A) at amino acid position 686 to be replaced by a proline (P). 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	0.087
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	.;.;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.1	.;.;.;L
MutationTaster	Benign	0.59	D;D;D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.71	N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.41	T;T;T;T
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.78	P;.;P;P
Vest4		0.44
MutPred		0.37		.;.;.;Gain of glycosylation at A710 (P = 0.0161);
MVP		0.58
ClinPred		0.28	T
GERP RS		0.39
Varity_R		0.10
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-139747047; COSMIC: COSV50199390; COSMIC: COSV50199390;