7-151066518-A-C

Position:

• chr7-151066518-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003040.4(SLC4A2):​c.580A>C​(p.Thr194Pro) variant causes a missense, splice region 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. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: SLC4A2 NM_003040.4 missense, splice_region
• Scores: Splicing: ADA: 0.00003403
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.498

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044795334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.580A>C	p.Thr194Pro	missense_variant, splice_region_variant	6/23	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.580A>C	p.Thr194Pro	missense_variant, splice_region_variant	6/23		NP_001186621.1
SLC4A2	NM_001199693.1	c.553A>C	p.Thr185Pro	missense_variant, splice_region_variant	5/22		NP_001186622.1
SLC4A2	NM_001199694.2	c.538A>C	p.Thr180Pro	missense_variant, splice_region_variant	5/22		NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.580A>C	p.Thr194Pro	missense_variant, splice_region_variant	6/23	1	NM_003040.4	ENSP00000405600	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 35

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

Mar 19, 2024

The c.580A>C (p.T194P) alteration is located in exon 6 (coding exon 5) of the SLC4A2 gene. This alteration results from a A to C substitution at nucleotide position 580, causing the threonine (T) at amino acid position 194 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	0.057
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.6
DANN	Benign	0.48
DEOGEN2	Benign	0.068	T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	.;T;T;T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.045	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.56	N;N;N;N
REVEL	Benign	0.10
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.066
MutPred		0.17		Loss of phosphorylation at T194 (P = 0.0413);Loss of phosphorylation at T194 (P = 0.0413);.;.;
MVP		0.25
MPC		0.65
ClinPred		0.060	T
GERP RS		0.48
Varity_R		0.11
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0
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: chr7-150763605;