17-7042044-C-T

Variant names:

• chr17-7042044-C-T
• rs761962811
• NM_001370549.1:c.1066G>A

Variant summary

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

The NM_001370549.1(SLC16A11):​c.1066G>A​(p.Val356Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,443,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V356L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.941
• Publications: 1 publications found

Genes affected

SLC16A11 (HGNC:23093): (solute carrier family 16 member 11) Enables pyruvate transmembrane transporter activity. Involved in lipid metabolic process. Located in endoplasmic reticulum membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13942575).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370549.1. 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
	SLC16A11	NM_001370549.1	MANE Select	c.1066G>A	p.Val356Met	missense	Exon 4 of 5	NP_001357478.1	I3L431
	SLC16A11	NM_153357.3		c.1066G>A	p.Val356Met	missense	Exon 3 of 4	NP_699188.2	I3L431
	SLC16A11	NM_001370553.1		c.1066G>A	p.Val356Met	missense	Exon 4 of 4	NP_001357482.1	A0A669KBK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A11	ENST00000574600.3	TSL:3 MANE Select	c.1066G>A	p.Val356Met	missense	Exon 4 of 5	ENSP00000460927.2	I3L431
	SLC16A11	ENST00000573338.1	TSL:1	n.678-136G>A		intron	N/A
	SLC16A11	ENST00000662352.3		c.1066G>A	p.Val356Met	missense	Exon 3 of 4	ENSP00000499634.1	I3L431

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000425 AC: 1 AN: 235114 AF XY: 0.00000784

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000952

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000194 AC: 28 AN: 1443452 Hom.: 0 Cov.: 32 AF XY: 0.0000168 AC XY: 12 AN XY: 715772

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.00 AC: 0 AN: 43168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.00 AC: 0 AN: 84076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.0000245 AC: 27 AN: 1101028

Other (OTH) AF: 0.0000168 AC: 1 AN: 59442

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.94
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.044
Sift	Benign	0.14	T
Sift4G	Benign	0.10	T
Polyphen		0.017	B
Vest4		0.11
MutPred		0.54		Loss of catalytic residue at V380 (P = 0.0024)
MVP		0.12
MPC		0.37
ClinPred		0.32	T
GERP RS		3.8
Varity_R		0.073
gMVP		0.38
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761962811; hg19: chr17-6945363;