chr7-151061996-C-G

Position:

• chr7-151061996-C-G

Variant summary

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

The NM_003040.4(SLC4A2):​c.9C>G​(p.Ser3Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC4A2 NM_003040.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

LOC128092247 (HGNC:):

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=0.15173826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.9C>G	p.Ser3Arg	missense_variant	2/23	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.9C>G	p.Ser3Arg	missense_variant	2/23		NP_001186621.1
LOC128092247	NM_001414898.1			downstream_gene_variant		ENST00000674552.1	NP_001401827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.9C>G	p.Ser3Arg	missense_variant	2/23	1	NM_003040.4	ENSP00000405600	P1
	ENST00000674552.1			downstream_gene_variant			NM_001414898.1	ENSP00000501917	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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 28, 2024

The c.9C>G (p.S3R) alteration is located in exon 2 (coding exon 1) of the SLC4A2 gene. This alteration results from a C to G substitution at nucleotide position 9, causing the serine (S) at amino acid position 3 to be replaced by an arginine (R). 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	0.19
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T;T;T;T;.;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.072
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.77	T;.;T;T;T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.0	.;N;N;.;.;.;.
MutationTaster	Benign	0.95	N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N
REVEL	Benign	0.057
Sift	Uncertain	0.0040	D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		0.30	.;B;B;.;.;.;.
Vest4		0.47, 0.45
MutPred		0.15		Loss of phosphorylation at S3 (P = 0.0042);Loss of phosphorylation at S3 (P = 0.0042);Loss of phosphorylation at S3 (P = 0.0042);Loss of phosphorylation at S3 (P = 0.0042);Loss of phosphorylation at S3 (P = 0.0042);Loss of phosphorylation at S3 (P = 0.0042);Loss of phosphorylation at S3 (P = 0.0042);
MVP		0.46
MPC		0.58
ClinPred		0.50	T
GERP RS		3.8
Varity_R		0.15
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-150759083;