20-46735127-T-C

Variant names:

• chr20-46735127-T-C
• rs707507
• NM_030777.4:c.*1293T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030777.4(SLC2A10):​c.*1293T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,528 control chromosomes in the GnomAD database, including 12,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12065 hom., cov: 32)
  • Exomes 𝑓: 0.40 (33 hom.)
• Consequence: SLC2A10 NM_030777.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17
• Publications: 10 publications found

Genes affected

SLC2A10 (HGNC:13444): (solute carrier family 2 member 10) This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]

SLC2A10 Gene-Disease associations (from GenCC):

• arterial tortuosity syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 20-46735127-T-C is Benign according to our data. Variant chr20-46735127-T-C is described in ClinVar as Benign. ClinVar VariationId is 338623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030777.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	NM_030777.4	MANE Select	c.*1293T>C		3_prime_UTR	Exon 5 of 5	NP_110404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.*1293T>C		3_prime_UTR	Exon 5 of 5	ENSP00000352216.2
	SLC2A10	ENST00000862794.1		c.*1293T>C		3_prime_UTR	Exon 5 of 5	ENSP00000532853.1
	SLC2A10	ENST00000862792.1		c.*1293T>C		3_prime_UTR	Exon 6 of 6	ENSP00000532851.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58879 AN: 151956 Hom.: 12041 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.414

GnomAD4 exome AF: 0.396 AC: 180 AN: 454 Hom.: 33 Cov.: 0 AF XY: 0.391 AC XY: 108 AN XY: 276

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.393 AC: 162 AN: 412

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.467 AC: 14 AN: 30

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.388 AC: 58938 AN: 152074 Hom.: 12065 Cov.: 32 AF XY: 0.392 AC XY: 29154 AN XY: 74332

African (AFR) AF: 0.262 AC: 10860 AN: 41488

American (AMR) AF: 0.450 AC: 6875 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3470

East Asian (EAS) AF: 0.586 AC: 3023 AN: 5160

South Asian (SAS) AF: 0.400 AC: 1927 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4547 AN: 10580

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28851 AN: 67978

Other (OTH) AF: 0.415 AC: 870 AN: 2098

Alfa AF: 0.414 Hom.: 16711

Bravo AF: 0.384

Asia WGS AF: 0.452 AC: 1569 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Arterial tortuosity syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.20
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs707507; hg19: chr20-45363766;