12-51425013-C-T

Variant names:

• chr12-51425013-C-T
• rs555252532
• NM_001039960.3:c.26C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001039960.3(SLC4A8):​c.26C>T​(p.Pro9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,556,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (1 hom.)
• Consequence: SLC4A8 NM_001039960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 0 publications found

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]

SLC4A8-AS1 (HGNC:55259): (SLC4A8 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033285975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039960.3. 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
	SLC4A8	NM_001039960.3	MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 25	NP_001035049.1	Q2Y0W8-1
	SLC4A8	NM_001405268.1		c.26C>T	p.Pro9Leu	missense	Exon 1 of 23	NP_001392197.1
	SLC4A8	NM_001258402.2		c.26C>T	p.Pro9Leu	missense	Exon 1 of 15	NP_001245331.1	Q2Y0W8-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A8	ENST00000453097.7	TSL:1 MANE Select	c.26C>T	p.Pro9Leu	missense	Exon 1 of 25	ENSP00000405812.2	Q2Y0W8-1
	SLC4A8	ENST00000358657.7	TSL:1	c.-111-15695C>T		intron	N/A	ENSP00000351483.4	Q2Y0W8-5
	SLC4A8	ENST00000877857.1		c.26C>T	p.Pro9Leu	missense	Exon 1 of 26	ENSP00000547916.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000955 AC: 15 AN: 157102 AF XY: 0.000130

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000399 AC: 56 AN: 1404306 Hom.: 1 Cov.: 31 AF XY: 0.0000447 AC XY: 31 AN XY: 693428

African (AFR) AF: 0.00 AC: 0 AN: 31826

American (AMR) AF: 0.00 AC: 0 AN: 36910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25226

East Asian (EAS) AF: 0.00 AC: 0 AN: 36140

South Asian (SAS) AF: 0.000465 AC: 37 AN: 79610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5272

European-Non Finnish (NFE) AF: 0.0000148 AC: 16 AN: 1082746

Other (OTH) AF: 0.0000516 AC: 3 AN: 58152

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000709 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.4
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.077
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.67	P
Vest4		0.24
MutPred		0.21		Loss of disorder (P = 0.026)
MVP		0.068
MPC		0.87
ClinPred		0.089	T
GERP RS		1.8
PromoterAI		-0.052	Neutral
Varity_R		0.080
gMVP		0.33
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs555252532; hg19: chr12-51818797;