Genetic Variant SLC16A8:p.Met359Thr (chr22-38080962-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013356.3(SLC16A8):c.1076T>C(p.Met359Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000901 in 1,443,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

SLC16A8
NM_013356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32782263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A8	NM_013356.3 link	c.1076T>C	p.Met359Thr	missense_variant	Exon 5 of 6	ENST00000681075.2	NP_037488.2	O95907
SLC16A8	XM_017028685.2 link	c.1076T>C	p.Met359Thr	missense_variant	Exon 3 of 4		XP_016884174.1	O95907
SLC16A8	NM_001394131.1 link	c.-80-2258T>C		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.1076T>C	p.Met359Thr	missense_variant	Exon 5 of 6		NM_013356.3	ENSP00000506669.1	O95907
SLC16A8	ENST00000320521.10 link	c.1076T>C	p.Met359Thr	missense_variant	Exon 4 of 5	1		ENSP00000321735.5	O95907
SLC16A8	ENST00000469516.5 link	n.107-2258T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000483

AC:

AN:

207228

Hom.:

AF XY:

0.0000261

AC XY:

AN XY:

114876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000282

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:

0.000187

GnomAD4 exome

AF:

0.00000901

AC:

AN:

1443122

Hom.:

Cov.:

AF XY:

0.00000836

AC XY:

AN XY:

717312

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000338

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1076T>C (p.M359T) alteration is located in exon 4 (coding exon 3) of the SLC16A8 gene. This alteration results from a T to C substitution at nucleotide position 1076, causing the methionine (M) at amino acid position 359 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.23

Sift

Benign

0.26

Sift4G

Benign

0.23

Polyphen

0.94

Vest4

0.56

MutPred

0.61

Gain of catalytic residue at M359 (P = 0.0184);

MVP

0.40

MPC

0.70

ClinPred

0.58

GERP RS

3.3

Varity_R

0.28

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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