Genetic Variant SLC16A8:p.Val387Met (chr22-38080879-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013356.3(SLC16A8):c.1159G>A(p.Val387Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,549,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC16A8
NM_013356.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.158

Variant links:

Genes affected

SLC16A8 (HGNC:16270): (solute carrier family 16 member 8) SLC16A8 is a member of a family of proton-coupled monocarboxylate transporters that mediate lactate transport across cell membranes (Yoon et al., 1999 [PubMed 10493836]).[supplied by OMIM, Apr 2010]

SLC16A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.05792868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A8	NM_013356.3 link	c.1159G>A	p.Val387Met	missense_variant	Exon 5 of 6	ENST00000681075.2	NP_037488.2	O95907
SLC16A8	XM_017028685.2 link	c.1159G>A	p.Val387Met	missense_variant	Exon 3 of 4		XP_016884174.1	O95907
SLC16A8	NM_001394131.1 link	c.-80-2175G>A		intron_variant	Intron 1 of 1		NP_001381060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC16A8	ENST00000681075.2 link	c.1159G>A	p.Val387Met	missense_variant	Exon 5 of 6		NM_013356.3	ENSP00000506669.1	O95907
SLC16A8	ENST00000320521.10 link	c.1159G>A	p.Val387Met	missense_variant	Exon 4 of 5	1		ENSP00000321735.5	O95907
SLC16A8	ENST00000469516.5 link	n.107-2175G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

149852

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

82690

show subpopulations

Gnomad AFR exome

AF:

0.000236

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000143

AC:

AN:

1397566

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691166

show subpopulations

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:

0.0000125

Gnomad4 FIN exome

AF:

0.0000267

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000261

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.5

DANN

Benign

0.94

DEOGEN2

Benign

0.059

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.70

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.3

REVEL

Benign

0.23

Sift

Benign

0.22

Sift4G

Benign

0.23

Polyphen

0.30

Vest4

0.17

MutPred

0.63

Loss of catalytic residue at V387 (P = 0.1357);

MVP

0.20

MPC

0.34

ClinPred

0.033

GERP RS

-6.2

Varity_R

0.057

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over