dbSNP rs387907524: SLC4A2:p.Pro18Leu (chr7-151064203-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003040.4(SLC4A2):c.53C>T(p.Pro18Leu) 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 30)

Consequence

SLC4A2
NM_003040.4 missense, splice_region

Scores

Splicing: ADA: 0.004354

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.05

Publications

1 publications found

Variant links:

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]

SLC4A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34082687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A2	NM_003040.4	MANE Select	c.53C>T	p.Pro18Leu	missense splice_region	Exon 3 of 23	NP_003031.3
SLC4A2	NM_001199692.3		c.53C>T	p.Pro18Leu	missense splice_region	Exon 3 of 23	NP_001186621.1	P04920-1
SLC4A2	NM_001199693.1		c.26C>T	p.Pro9Leu	missense splice_region	Exon 2 of 22	NP_001186622.1	Q59GF1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.53C>T	p.Pro18Leu	missense splice_region	Exon 3 of 23	ENSP00000405600.2	P04920-1
SLC4A2	ENST00000485713.6	TSL:1	c.53C>T	p.Pro18Leu	missense splice_region	Exon 3 of 23	ENSP00000419412.1
SLC4A2	ENST00000461735.1	TSL:1	c.11C>T	p.Pro4Leu	missense splice_region	Exon 2 of 22	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.17

MutationAssessor

Uncertain

2.1

PhyloP100

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

REVEL

Benign

0.15

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.20

MutPred

0.12

Loss of relative solvent accessibility (P = 0.0414)

MVP

0.46

MPC

0.51

ClinPred

0.33

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.78

Mutation Taster

=43/57

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0044

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.10

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