17-7042350-C-T

Variant names:

• chr17-7042350-C-T
• rs200478682
• NM_001370549.1:c.760G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001370549.1(SLC16A11):​c.760G>A​(p.Gly254Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,558,692 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 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. G254E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (2 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.898
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019336224).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.760G>A	p.Gly254Arg	missense	Exon 4 of 5	NP_001357478.1	I3L431
	SLC16A11	NM_153357.3		c.760G>A	p.Gly254Arg	missense	Exon 3 of 4	NP_699188.2	I3L431
	SLC16A11	NM_001370553.1		c.760G>A	p.Gly254Arg	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.760G>A	p.Gly254Arg	missense	Exon 4 of 5	ENSP00000460927.2	I3L431
	SLC16A11	ENST00000573338.1	TSL:1	n.678-442G>A		intron	N/A
	SLC16A11	ENST00000662352.3		c.760G>A	p.Gly254Arg	missense	Exon 3 of 4	ENSP00000499634.1	I3L431

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000735

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000395 AC: 66 AN: 166940 AF XY: 0.000392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000706

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.000429 AC: 604 AN: 1406504 Hom.: 2 Cov.: 32 AF XY: 0.000405 AC XY: 281 AN XY: 694290

African (AFR) AF: 0.0000313 AC: 1 AN: 31972

American (AMR) AF: 0.000394 AC: 15 AN: 38030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25038

East Asian (EAS) AF: 0.00 AC: 0 AN: 36460

South Asian (SAS) AF: 0.0000250 AC: 2 AN: 80000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48848

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5678

European-Non Finnish (NFE) AF: 0.000515 AC: 557 AN: 1082356

Other (OTH) AF: 0.000396 AC: 23 AN: 58122

GnomAD4 genome AF: 0.000375 AC: 57 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74346

African (AFR) AF: 0.0000483 AC: 2 AN: 41432

American (AMR) AF: 0.000262 AC: 4 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68038

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000493 Hom.: 2

Bravo AF: 0.000317

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000353 AC: 3

ExAC AF: 0.000162 AC: 19

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	Benign	0.086
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.90
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.072
Sift	Benign	0.73	T
Sift4G	Benign	0.74	T
Polyphen		0.047	B
Vest4		0.13
MutPred		0.64		Gain of methylation at G278 (P = 0.0172)
MVP		0.37
MPC		0.63
ClinPred		0.077	T
GERP RS		4.0
Varity_R		0.16
gMVP		0.58
Mutation Taster		=69/31	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: rs200478682; hg19: chr17-6945669; COSMIC: COSV100338767; COSMIC: COSV100338767;