rs13342692

Positions:

• chr17-7042968-T-C
• chr17-7042968-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370549.1(SLC16A11):​c.308A>G​(p.Asp103Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,612,368 control chromosomes in the GnomAD database, including 7,567 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2819 hom., cov: 33)
  • Exomes 𝑓: 0.031 (4748 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.276

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0112018585).
• BP6: Variant 17-7042968-T-C is Benign according to our data. Variant chr17-7042968-T-C is described in ClinVar as [Benign]. Clinvar id is 1182780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A11	NM_001370549.1	c.308A>G	p.Asp103Gly	missense_variant	3/5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3	c.308A>G	p.Asp103Gly	missense_variant	2/4		NP_699188.2
SLC16A11	NM_001370553.1	c.308A>G	p.Asp103Gly	missense_variant	3/4		NP_001357482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A11	ENST00000574600.3	c.308A>G	p.Asp103Gly	missense_variant	3/5	3	NM_001370549.1	ENSP00000460927	P1
SLC16A11	ENST00000573338.1	n.639A>G		non_coding_transcript_exon_variant	1/2	1
SLC16A11	ENST00000662352.3	c.308A>G	p.Asp103Gly	missense_variant	2/4			ENSP00000499634	P1
SLC16A11	ENST00000673828.2	c.308A>G	p.Asp103Gly	missense_variant	3/4			ENSP00000501313

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18704 AN: 152090 Hom.: 2796 Cov.: 33

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.0819 AC: 20111 AN: 245446 Hom.: 2865 AF XY: 0.0640 AC XY: 8568 AN XY: 133806

Gnomad AFR exome AF: 0.340

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.0376

Gnomad EAS exome AF: 0.0965

Gnomad SAS exome AF: 0.00600

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.0595

GnomAD4 exome AF: 0.0308 AC: 44923 AN: 1460160 Hom.: 4748 Cov.: 32 AF XY: 0.0278 AC XY: 20225 AN XY: 726342

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.0380

Gnomad4 EAS exome AF: 0.0862

Gnomad4 SAS exome AF: 0.00636

Gnomad4 FIN exome AF: 0.0189

Gnomad4 NFE exome AF: 0.00998

Gnomad4 OTH exome AF: 0.0460

GnomAD4 genome AF: 0.123 AC: 18778 AN: 152208 Hom.: 2819 Cov.: 33 AF XY: 0.123 AC XY: 9123 AN XY: 74414

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0360 Hom.: 1324

Bravo AF: 0.151

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.305 AC: 1343

ESP6500EA AF: 0.0126 AC: 108

ExAC AF: 0.0753 AC: 9126

Asia WGS AF: 0.0650 AC: 225 AN: 3478

EpiCase AF: 0.0129

EpiControl AF: 0.0130

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 31118516) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.12	T;T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.26	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.11
Sift	Benign	0.044	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		0.0010	B;.
Vest4		0.055
MPC		0.43
ClinPred		0.0049	T
GERP RS		5.2
Varity_R		0.080
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13342692; hg19: chr17-6946287; COSMIC: COSV57273658; COSMIC: COSV57273658;