rs1950693575

Variant names:

• chr12-51471379-C-A
• rs1950693575
• NM_001039960.3:c.1751C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-51471379-C-A
• chr12-51471379-C-T

Variant summary

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

The NM_001039960.3(SLC4A8):​c.1751C>A​(p.Ser584Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S584F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A8 NM_001039960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• 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 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1751C>A	p.Ser584Tyr	missense	Exon 14 of 25	NP_001035049.1	Q2Y0W8-1
	SLC4A8	NM_001405270.1		c.1715C>A	p.Ser572Tyr	missense	Exon 14 of 25	NP_001392199.1
	SLC4A8	NM_001258401.3		c.1592C>A	p.Ser531Tyr	missense	Exon 14 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.1751C>A	p.Ser584Tyr	missense	Exon 14 of 25	ENSP00000405812.2	Q2Y0W8-1
	SLC4A8	ENST00000358657.7	TSL:1	c.1592C>A	p.Ser531Tyr	missense	Exon 14 of 25	ENSP00000351483.4	Q2Y0W8-5
	SLC4A8	ENST00000514353.7	TSL:1	c.1592C>A	p.Ser531Tyr	missense	Exon 14 of 17	ENSP00000442561.2	Q2Y0W8-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	28
DANN	Benign	0.94
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.8
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.60
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.56		Loss of glycosylation at S584 (P = 0.0735)
MVP		0.55
MPC		1.9
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.51
gMVP		0.90
Mutation Taster		=39/61	disease causing

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: rs1950693575; hg19: chr12-51865163;