NM_003759.4:c.15T>A

Variant names:

• chr4-71339263-T-A
• NM_003759.4:c.15T>A

Variant summary

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

The NM_003759.4(SLC4A4):​c.15T>A​(p.Asn5Lys) 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. 13/15 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: 32)
• Consequence: SLC4A4 NM_003759.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

Genes affected

SLC4A4 (HGNC:11030): (solute carrier family 4 member 4) This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

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=0.030153573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_003759.4	c.15T>A	p.Asn5Lys	missense_variant	Exon 1 of 23	ENST00000340595.4	NP_003750.1
SLC4A4	NM_001098484.3	c.254-107T>A		intron_variant	Intron 3 of 25	ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000340595.4	c.15T>A	p.Asn5Lys	missense_variant	Exon 1 of 23	1	NM_003759.4	ENSP00000344272.3
SLC4A4	ENST00000264485.11	c.254-107T>A		intron_variant	Intron 3 of 25	1	NM_001098484.3	ENSP00000264485.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.81
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.030	T;T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	0.85	N;N
REVEL	Benign	0.062
Sift	Benign	0.25	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0010	B;B
Vest4		0.083
MutPred		0.14		Gain of ubiquitination at N5 (P = 0.001);Gain of ubiquitination at N5 (P = 0.001);
MVP		0.16
ClinPred		0.038	T
GERP RS		0.52

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: chr4-72204980;