17-7042358-C-T

Variant names:

• chr17-7042358-C-T
• rs1484890245
• NM_001370549.1:c.752G>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.752G>A​(p.Gly251Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000512 in 1,563,128 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. G251A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• 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=0.13964817).

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.752G>A	p.Gly251Glu	missense	Exon 4 of 5	NP_001357478.1	I3L431
	SLC16A11	NM_153357.3		c.752G>A	p.Gly251Glu	missense	Exon 3 of 4	NP_699188.2	I3L431
	SLC16A11	NM_001370553.1		c.752G>A	p.Gly251Glu	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.752G>A	p.Gly251Glu	missense	Exon 4 of 5	ENSP00000460927.2	I3L431
	SLC16A11	ENST00000573338.1	TSL:1	n.678-450G>A		intron	N/A
	SLC16A11	ENST00000662352.3		c.752G>A	p.Gly251Glu	missense	Exon 3 of 4	ENSP00000499634.1	I3L431

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32

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 AF: 0.00000496 AC: 7 AN: 1410914 Hom.: 0 Cov.: 32 AF XY: 0.00000287 AC XY: 2 AN XY: 697164

African (AFR) AF: 0.00 AC: 0 AN: 32096

American (AMR) AF: 0.00 AC: 0 AN: 38464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25216

East Asian (EAS) AF: 0.00 AC: 0 AN: 36632

South Asian (SAS) AF: 0.00 AC: 0 AN: 80334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000553 AC: 6 AN: 1085054

Other (OTH) AF: 0.0000171 AC: 1 AN: 58318

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74360

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.27	N
PhyloP100		0.10
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.25
Sift	Benign	0.19	T
Sift4G	Benign	0.19	T
Polyphen		0.96	D
Vest4		0.14
MutPred		0.40		Gain of solvent accessibility (P = 0.0456)
MVP		0.50
MPC		0.45
ClinPred		0.69	D
GERP RS		4.1
Varity_R		0.054
gMVP		0.36
Mutation Taster		=85/15	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: rs1484890245; hg19: chr17-6945677; COSMIC: COSV57274921; COSMIC: COSV57274921;