Genetic Variant SLC4A8:p.Ile187Val (chr12-51453684-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039960.3(SLC4A8):c.559A>G(p.Ile187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.0000014 ( 0 hom. )

Consequence

SLC4A8
NM_001039960.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.631

Publications

0 publications found

Variant links:

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)

SLC4A8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.13348716).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A8	NM_001039960.3	MANE Select	c.559A>G	p.Ile187Val	missense	Exon 5 of 25	NP_001035049.1	Q2Y0W8-1
SLC4A8	NM_001405270.1		c.523A>G	p.Ile175Val	missense	Exon 5 of 25	NP_001392199.1
SLC4A8	NM_001258401.3		c.400A>G	p.Ile134Val	missense	Exon 5 of 25	NP_001245330.1	Q2Y0W8-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC4A8	ENST00000453097.7	TSL:1 MANE Select	c.559A>G	p.Ile187Val	missense	Exon 5 of 25	ENSP00000405812.2	Q2Y0W8-1
SLC4A8	ENST00000358657.7	TSL:1	c.400A>G	p.Ile134Val	missense	Exon 5 of 25	ENSP00000351483.4	Q2Y0W8-5
SLC4A8	ENST00000514353.7	TSL:1	c.400A>G	p.Ile134Val	missense	Exon 5 of 17	ENSP00000442561.2	Q2Y0W8-7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250400

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.00000137

AC:

AN:

1460652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726476

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111322

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.84

M_CAP

Benign

0.019

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.1

PhyloP100

0.63

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.90

REVEL

Benign

0.21

Sift

Benign

0.030

Sift4G

Uncertain

0.040

Polyphen

0.36

Vest4

0.18

MutPred

0.71

Loss of phosphorylation at S186 (P = 0.1948)

MVP

0.082

MPC

0.57

ClinPred

0.43

GERP RS

4.3

Varity_R

0.41

gMVP

0.21

Mutation Taster

=70/30

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over