rs1193232489

Variant names:

• chr17-7042401-G-A
• rs1193232489
• NM_001370549.1:c.709C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001370549.1(SLC16A11):​c.709C>T​(p.Pro237Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000192 in 1,562,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.46
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

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.709C>T	p.Pro237Ser	missense	Exon 4 of 5	NP_001357478.1	I3L431
	SLC16A11	NM_153357.3		c.709C>T	p.Pro237Ser	missense	Exon 3 of 4	NP_699188.2	I3L431
	SLC16A11	NM_001370553.1		c.709C>T	p.Pro237Ser	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.709C>T	p.Pro237Ser	missense	Exon 4 of 5	ENSP00000460927.2	I3L431
	SLC16A11	ENST00000573338.1	TSL:1	n.678-493C>T		intron	N/A
	SLC16A11	ENST00000662352.3		c.709C>T	p.Pro237Ser	missense	Exon 3 of 4	ENSP00000499634.1	I3L431

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000595 AC: 1 AN: 167930 AF XY: 0.00

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: 0.0000153

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1410590 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 696948

African (AFR) AF: 0.00 AC: 0 AN: 32150

American (AMR) AF: 0.00 AC: 0 AN: 37868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25324

East Asian (EAS) AF: 0.00 AC: 0 AN: 36704

South Asian (SAS) AF: 0.00 AC: 0 AN: 80424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1084788

Other (OTH) AF: 0.00 AC: 0 AN: 58398

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.62		Loss of sheet (P = 0.0357)
MVP		0.79
MPC		1.1
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.73
gMVP		0.79
Mutation Taster		=27/73	disease causing

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: rs1193232489; hg19: chr17-6945720;