rs749911186

Variant names:

• chr12-51475175-C-T
• rs749911186
• NM_001039960.3:c.2141C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-51475175-C-T
• chr12-51475175-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039960.3(SLC4A8):​c.2141C>T​(p.Thr714Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SLC4A8 NM_001039960.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.983
• Publications: 3 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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23147896).

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.2141C>T	p.Thr714Met	missense	Exon 16 of 25	NP_001035049.1	Q2Y0W8-1
	SLC4A8	NM_001405270.1		c.2105C>T	p.Thr702Met	missense	Exon 16 of 25	NP_001392199.1
	SLC4A8	NM_001258401.3		c.1982C>T	p.Thr661Met	missense	Exon 16 of 25	NP_001245330.1	Q2Y0W8-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A8	ENST00000453097.7	TSL:1 MANE Select	c.2141C>T	p.Thr714Met	missense	Exon 16 of 25	ENSP00000405812.2	Q2Y0W8-1
	SLC4A8	ENST00000358657.7	TSL:1	c.1982C>T	p.Thr661Met	missense	Exon 16 of 25	ENSP00000351483.4	Q2Y0W8-5
	SLC4A8	ENST00000514353.7	TSL:1	c.1982C>T	p.Thr661Met	missense	Exon 16 of 17	ENSP00000442561.2	Q2Y0W8-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251028 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 727174

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26118

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111896

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000247 AC: 3

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	0.070
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.097
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.98
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.54	N
REVEL	Uncertain	0.34
Sift	Benign	0.031	D
Sift4G	Uncertain	0.044	D
Polyphen		0.15	B
Vest4		0.19
MutPred		0.43		Gain of MoRF binding (P = 0.0728)
MVP		0.043
MPC		0.72
ClinPred		0.25	T
GERP RS		5.6
Varity_R		0.039
gMVP		0.60
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs749911186; hg19: chr12-51868959;