rs777593474

Variant names:

• chr12-51453684-A-C
• NM_001039960.3:c.559A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-51453684-A-C
• chr12-51453684-A-G

Variant summary

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

The NM_001039960.3(SLC4A8):​c.559A>C​(p.Ile187Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC4A8 NM_001039960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

Genes affected

SLC4A8 (HGNC:11034): (solute carrier family 4 member 8) The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

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=0.054930955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A8	NM_001039960.3	c.559A>C	p.Ile187Leu	missense_variant	Exon 5 of 25	ENST00000453097.7	NP_001035049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A8	ENST00000453097.7	c.559A>C	p.Ile187Leu	missense_variant	Exon 5 of 25	1	NM_001039960.3	ENSP00000405812.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460652 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726476

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.69
DEOGEN2	Benign	0.13	.;.;T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.055	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	.;.;N;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.69	N;.;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;.;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0030	.;.;B;.
Vest4		0.24
MutPred		0.66		.;.;Gain of disorder (P = 0.1171);.;
MVP		0.043
MPC		0.72
ClinPred		0.22	T
GERP RS		4.3
Varity_R		0.50
gMVP		0.42

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: chr12-51847468;