22-38078413-G-C

Variant names:

• chr22-38078413-G-C
• rs371969955
• NM_013356.3:c.1490C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013356.3(SLC16A8):​c.1490C>G​(p.Pro497Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P497L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: SLC16A8 NM_013356.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07963437).

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.1490C>G	p.Pro497Arg	missense	Exon 6 of 6	NP_037488.2	O95907
	SLC16A8	NM_001394131.1		c.212C>G	p.Pro71Arg	missense	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.1490C>G	p.Pro497Arg	missense	Exon 6 of 6	ENSP00000506669.1	O95907
	SLC16A8	ENST00000320521.10	TSL:1	c.1490C>G	p.Pro497Arg	missense	Exon 5 of 5	ENSP00000321735.5	O95907
	SLC16A8	ENST00000902580.1		c.1490C>G	p.Pro497Arg	missense	Exon 5 of 5	ENSP00000572639.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.4
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.86
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.024
Sift	Benign	0.12	T
Sift4G	Uncertain	0.019	D
Polyphen		0.19	B
Vest4		0.20
MutPred		0.30		Gain of MoRF binding (P = 0.0086)
MVP		0.23
MPC		0.38
ClinPred		0.17	T
GERP RS		1.8
Varity_R		0.022
gMVP		0.55
Mutation Taster		=87/13	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: rs371969955; hg19: chr22-38474420;