20-46724875-C-CGGACGGAT

Variant names:

• chr20-46724875-C-CGGACGGAT
• rs1555887757
• NM_030777.4:c.5-163_5-162insCGGATGGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_030777.4(SLC2A10):​c.5-163_5-162insCGGATGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0029 (3 hom., cov: 0)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234
• 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 -10 ACMG points.

• BP6: Variant 20-46724875-C-CGGACGGAT is Benign according to our data. Variant chr20-46724875-C-CGGACGGAT is described in ClinVar as [Likely_benign]. Clinvar id is 1212798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00287 (401/139876) while in subpopulation AFR AF = 0.0105 (381/36292). AF 95% confidence interval is 0.00963. There are 3 homozygotes in GnomAd4. There are 186 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.5-163_5-162insCGGATGGA		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.5-166_5-165insGGACGGAT		intron_variant	Intron 1 of 4	1	NM_030777.4	ENSP00000352216.2
SLC2A10	ENST00000611837.1	n.157-166_157-165insGGACGGAT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.00287 AC: 401 AN: 139760 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000349

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000223

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000153

Gnomad OTH AF: 0.00156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00287 AC: 401 AN: 139876 Hom.: 3 Cov.: 0 AF XY: 0.00274 AC XY: 186 AN XY: 67814

African (AFR) AF: 0.0105 AC: 381 AN: 36292

American (AMR) AF: 0.000349 AC: 5 AN: 14344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3386

East Asian (EAS) AF: 0.000223 AC: 1 AN: 4478

South Asian (SAS) AF: 0.00 AC: 0 AN: 4080

European-Finnish (FIN) AF: 0.000112 AC: 1 AN: 8902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.000153 AC: 10 AN: 65306

Other (OTH) AF: 0.00154 AC: 3 AN: 1950

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 21, 2019

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
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs1555887757; hg19: chr20-45353514;