20-46709968-C-T

Variant names:

• chr20-46709968-C-T
• rs181896882
• NM_030777.4:c.4+228C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030777.4(SLC2A10):​c.4+228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 557,940 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.758
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 20-46709968-C-T is Benign according to our data. Variant chr20-46709968-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1223421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00477 (726/152336) while in subpopulation AFR AF = 0.0161 (668/41582). AF 95% confidence interval is 0.0151. There are 4 homozygotes in GnomAd4. There are 366 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.4+228C>T		intron_variant	Intron 1 of 4	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4	c.4+228C>T		intron_variant	Intron 1 of 4	1	NM_030777.4	ENSP00000352216.2
SLC2A10	ENST00000486000.2	c.5-15C>T		intron_variant	Intron 1 of 1	3		ENSP00000478679.1

Frequencies

GnomAD3 genomes AF: 0.00478 AC: 727 AN: 152218 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

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: 0.000103

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000478 AC: 194 AN: 405604 Hom.: 1 Cov.: 4 AF XY: 0.000438 AC XY: 93 AN XY: 212540

African (AFR) AF: 0.0144 AC: 121 AN: 8406

American (AMR) AF: 0.00137 AC: 16 AN: 11662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12300

East Asian (EAS) AF: 0.00 AC: 0 AN: 24182

South Asian (SAS) AF: 0.00 AC: 0 AN: 39306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29474

Middle Eastern (MID) AF: 0.00110 AC: 2 AN: 1826

European-Non Finnish (NFE) AF: 0.0000904 AC: 23 AN: 254492

Other (OTH) AF: 0.00134 AC: 32 AN: 23956

GnomAD4 genome AF: 0.00477 AC: 726 AN: 152336 Hom.: 4 Cov.: 33 AF XY: 0.00491 AC XY: 366 AN XY: 74488

African (AFR) AF: 0.0161 AC: 668 AN: 41582

American (AMR) AF: 0.00300 AC: 46 AN: 15314

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00299 Hom.: 0

Bravo AF: 0.00545

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 03, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.89
PhyloP100		0.76
PromoterAI		0.19	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs181896882; hg19: chr20-45338607;