22-38078699-G-C

Variant names:

• chr22-38078699-G-C
• NM_013356.3:c.1204C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013356.3(SLC16A8):​c.1204C>G​(p.Leu402Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC16A8 NM_013356.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

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]

LOC105373027 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A8	NM_013356.3	c.1204C>G	p.Leu402Val	missense_variant	Exon 6 of 6	ENST00000681075.2	NP_037488.2
SLC16A8	XM_017028685.2	c.1204C>G	p.Leu402Val	missense_variant	Exon 4 of 4		XP_016884174.1
SLC16A8	NM_001394131.1	c.-75C>G		5_prime_UTR_variant	Exon 2 of 2		NP_001381060.1
LOC105373027	XR_938249.3	n.59G>C		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A8	ENST00000681075.2	c.1204C>G	p.Leu402Val	missense_variant	Exon 6 of 6		NM_013356.3	ENSP00000506669.1
SLC16A8	ENST00000320521.10	c.1204C>G	p.Leu402Val	missense_variant	Exon 5 of 5	1		ENSP00000321735.5
SLC16A8	ENST00000469516.5	n.112C>G		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1204C>G (p.L402V) alteration is located in exon 5 (coding exon 4) of the SLC16A8 gene. This alteration results from a C to G substitution at nucleotide position 1204, causing the leucine (L) at amino acid position 402 to be replaced by a valine (V). 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	Benign	0.26
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.38	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.074
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.021	D
Polyphen		0.95	P
Vest4		0.75
MutPred		0.31		Gain of methylation at R401 (P = 0.1085);
MVP		0.67
MPC		0.63
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.23
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-38474706;