22-38078669-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A8	NM_013356.3	c.1234A>C	p.Ile412Leu	missense_variant	Exon 6 of 6	ENST00000681075.2	NP_037488.2
SLC16A8	XM_017028685.2	c.1234A>C	p.Ile412Leu	missense_variant	Exon 4 of 4		XP_016884174.1
SLC16A8	NM_001394131.1	c.-45A>C		5_prime_UTR_variant	Exon 2 of 2		NP_001381060.1
LOC105373027	XR_938249.3	n.29T>G		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.1234A>C	p.Ile412Leu	missense_variant	Exon 6 of 6		NM_013356.3	ENSP00000506669.1
SLC16A8	ENST00000320521.10	c.1234A>C	p.Ile412Leu	missense_variant	Exon 5 of 5	1		ENSP00000321735.5
SLC16A8	ENST00000469516.5	n.142A>C		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1234A>C (p.I412L) alteration is located in exon 5 (coding exon 4) of the SLC16A8 gene. This alteration results from a A to C substitution at nucleotide position 1234, causing the isoleucine (I) at amino acid position 412 to be replaced by a leucine (L). 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	0.36
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
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

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: chr22-38474676;