22-38078701-C-A

Variant names:

• chr22-38078701-C-A
• rs777819488
• NM_013356.3:c.1202G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013356.3(SLC16A8):​c.1202G>T​(p.Arg401Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R401H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC16A8 NM_013356.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3532312).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013356.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A8	NM_013356.3	MANE Select	c.1202G>T	p.Arg401Leu	missense	Exon 6 of 6	NP_037488.2	O95907
	SLC16A8	NM_001394131.1		c.-77G>T		5_prime_UTR	Exon 2 of 2	NP_001381060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A8	ENST00000681075.2	MANE Select	c.1202G>T	p.Arg401Leu	missense	Exon 6 of 6	ENSP00000506669.1	O95907
	SLC16A8	ENST00000320521.10	TSL:1	c.1202G>T	p.Arg401Leu	missense	Exon 5 of 5	ENSP00000321735.5	O95907
	SLC16A8	ENST00000902580.1		c.1202G>T	p.Arg401Leu	missense	Exon 5 of 5	ENSP00000572639.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.78
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N
PhyloP100		0.74
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.25
Sift	Benign	0.45	T
Sift4G	Benign	0.64	T
Polyphen		0.033	B
Vest4		0.67
MutPred		0.61		Loss of methylation at R401 (P = 0.0325)
MVP		0.28
MPC		0.22
ClinPred		0.13	T
GERP RS		1.7
Varity_R		0.16
gMVP		0.48
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs777819488; hg19: chr22-38474708;