chr22-38078669-T-G

Variant names:

• chr22-38078669-T-G
• NM_013356.3:c.1234A>C

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.1234A>C​(p.Ile412Leu) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I412S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC16A8 NM_013356.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11099556).

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.1234A>C	p.Ile412Leu	missense	Exon 6 of 6	NP_037488.2	O95907
	SLC16A8	NM_001394131.1		c.-45A>C		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.1234A>C	p.Ile412Leu	missense	Exon 6 of 6	ENSP00000506669.1	O95907
	SLC16A8	ENST00000320521.10	TSL:1	c.1234A>C	p.Ile412Leu	missense	Exon 5 of 5	ENSP00000321735.5	O95907
	SLC16A8	ENST00000902580.1		c.1234A>C	p.Ile412Leu	missense	Exon 5 of 5	ENSP00000572639.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.074
Sift	Benign	0.21	T
Sift4G	Benign	0.33	T
Polyphen		0.0040	B
Vest4		0.22
MutPred		0.34		Loss of methylation at K407 (P = 0.1836)
MVP		0.27
MPC		0.17
ClinPred		0.38	T
GERP RS		4.9
Varity_R		0.13
gMVP		0.40
Mutation Taster		=73/27	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

hg19: chr22-38474676;