NM_003040.4:c.77G>T

Variant names:

• chr7-151064227-G-T
• rs2303929
• NM_003040.4:c.77G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003040.4(SLC4A2):​c.77G>T​(p.Gly26Val) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLC4A2 NM_003040.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• Publications: 47 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spherocytosis type 4

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• osteopetrosis, autosomal recessive 9

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044388473).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	NM_003040.4	MANE Select	c.77G>T	p.Gly26Val	missense	Exon 3 of 23	NP_003031.3
	SLC4A2	NM_001199692.3		c.77G>T	p.Gly26Val	missense	Exon 3 of 23	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.50G>T	p.Gly17Val	missense	Exon 2 of 22	NP_001186622.1	Q59GF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.77G>T	p.Gly26Val	missense	Exon 3 of 23	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.77G>T	p.Gly26Val	missense	Exon 3 of 23	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.35G>T	p.Gly12Val	missense	Exon 2 of 22	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.27
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.083	T
Sift4G	Uncertain	0.044	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.14		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.52
MPC		0.73
ClinPred		0.023	T
GERP RS		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.22
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2303929; hg19: chr7-150761314;