dbSNP rs187455529: SLC16A8:p.Glu502Lys (chr22-38078399-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_013356.3(SLC16A8):c.1504G>A(p.Glu502Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,599,468 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

SLC16A8
NM_013356.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.750

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:

LOC105373027 (HGNC:):

LOC105373027 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004611045).

BP6

Variant 22-38078399-C-T is Benign according to our data. Variant chr22-38078399-C-T is described in ClinVar as [Benign]. Clinvar id is 712401.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A8	NM_013356.3 link	c.1504G>A	p.Glu502Lys	missense_variant	Exon 6 of 6	ENST00000681075.2	NP_037488.2	O95907
SLC16A8	NM_001394131.1 link	c.226G>A	p.Glu76Lys	missense_variant	Exon 2 of 2		NP_001381060.1
SLC16A8	XM_017028685.2 link	c.1504G>A	p.Glu502Lys	missense_variant	Exon 4 of 4		XP_016884174.1	O95907
LOC105373027	XR_938249.3 link	n.-242C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC16A8	ENST00000681075.2 link	c.1504G>A	p.Glu502Lys	missense_variant	Exon 6 of 6		NM_013356.3	ENSP00000506669.1	O95907
SLC16A8	ENST00000320521.10 link	c.1504G>A	p.Glu502Lys	missense_variant	Exon 5 of 5	1		ENSP00000321735.5	O95907
SLC16A8	ENST00000469516.5 link	n.412G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00866

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000738

AC:

178

AN:

241224

Hom.:

AF XY:

0.000693

AC XY:

AN XY:

131360

show subpopulations

Gnomad AFR exome

AF:

0.0000641

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00901

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.000223

AC:

322

AN:

1447130

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

173

AN XY:

719404

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00493

Gnomad4 SAS exome

AF:

0.000535

Gnomad4 FIN exome

AF:

0.0000462

Gnomad4 NFE exome

AF:

0.00000722

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000407

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00868

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000541

Hom.:

Bravo

AF:

0.000457

ExAC

AF:

0.000725

AC:

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.029

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.32

REVEL

Benign

0.029

Sift

Benign

0.18

Sift4G

Benign

0.51

Polyphen

0.0010

Vest4

0.097

MVP

0.20

MPC

0.18

ClinPred

0.012

GERP RS

0.33

Varity_R

0.038

gMVP

0.38

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over