9-133475078-T-G

Variant names:

• chr9-133475078-T-G
• rs2073935
• NM_017585.4:c.810A>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017585.4(SLC2A6):​c.810A>C​(p.Pro270Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,593,342 control chromosomes in the GnomAD database, including 415,396 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34746 hom., cov: 36)
  • Exomes 𝑓: 0.72 (380650 hom.)
• Consequence: SLC2A6 NM_017585.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 17 publications found

Genes affected

SLC2A6 (HGNC:11011): (solute carrier family 2 member 6) Hexose transport into mammalian cells is catalyzed by a family of membrane proteins, including SLC2A6, that contain 12 transmembrane domains and a number of critical conserved residues.[supplied by OMIM, Jul 2002]

SLC2A6 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.879 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A6	NM_017585.4	c.810A>C	p.Pro270Pro	synonymous_variant	Exon 6 of 10	ENST00000371899.9	NP_060055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A6	ENST00000371899.9	c.810A>C	p.Pro270Pro	synonymous_variant	Exon 6 of 10	1	NM_017585.4	ENSP00000360966.4
SLC2A6	ENST00000371897.8	c.810A>C	p.Pro270Pro	synonymous_variant	Exon 6 of 9	2		ENSP00000360964.4
SLC2A6	ENST00000485978.1	n.1398A>C		non_coding_transcript_exon_variant	Exon 5 of 8	5

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101367 AN: 152074 Hom.: 34713 Cov.: 36

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.657

GnomAD2 exomes AF: 0.730 AC: 162084 AN: 221944 AF XY: 0.730

Gnomad AFR exome AF: 0.517

Gnomad AMR exome AF: 0.792

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.934

Gnomad FIN exome AF: 0.680

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.706

GnomAD4 exome AF: 0.724 AC: 1043724 AN: 1441148 Hom.: 380650 Cov.: 64 AF XY: 0.726 AC XY: 519228 AN XY: 715554

African (AFR) AF: 0.508 AC: 16829 AN: 33118

American (AMR) AF: 0.787 AC: 33477 AN: 42558

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 16078 AN: 25522

East Asian (EAS) AF: 0.913 AC: 35566 AN: 38956

South Asian (SAS) AF: 0.798 AC: 66703 AN: 83554

European-Finnish (FIN) AF: 0.692 AC: 33581 AN: 48532

Middle Eastern (MID) AF: 0.655 AC: 3355 AN: 5120

European-Non Finnish (NFE) AF: 0.720 AC: 795513 AN: 1104232

Other (OTH) AF: 0.716 AC: 42622 AN: 59556

GnomAD4 genome AF: 0.667 AC: 101453 AN: 152194 Hom.: 34746 Cov.: 36 AF XY: 0.671 AC XY: 49920 AN XY: 74420

African (AFR) AF: 0.519 AC: 21559 AN: 41500

American (AMR) AF: 0.739 AC: 11309 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2167 AN: 3470

East Asian (EAS) AF: 0.930 AC: 4815 AN: 5176

South Asian (SAS) AF: 0.812 AC: 3925 AN: 4832

European-Finnish (FIN) AF: 0.673 AC: 7135 AN: 10606

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48551 AN: 67996

Other (OTH) AF: 0.660 AC: 1393 AN: 2112

Alfa AF: 0.712 Hom.: 44654

Bravo AF: 0.662

Asia WGS AF: 0.844 AC: 2936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.61
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs2073935; hg19: chr9-136340200; COSMIC: COSV52469587; COSMIC: COSV52469587;