20-46724806-AGGATGGATGGATGGATGGAT-AGGATGGAT

Variant names:

• chr20-46724806-AGGATGGATGGAT-A
• rs111504264
• NM_030777.4:c.5-204_5-193delATGGATGGATGG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_030777.4(SLC2A10):​c.5-204_5-193delATGGATGGATGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 125,694 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0012 (1 hom., cov: 26)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00119 (150/125694) while in subpopulation AFR AF = 0.00335 (108/32250). AF 95% confidence interval is 0.00284. There are 1 homozygotes in GnomAd4. There are 62 alleles in the male GnomAd4 subpopulation. Median coverage is 26. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A10	NM_030777.4	c.5-204_5-193delATGGATGGATGG		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.5-234_5-223delGGATGGATGGAT		intron_variant	Intron 1 of 4	1	NM_030777.4	ENSP00000352216.2
SLC2A10	ENST00000611837.1	n.157-234_157-223delGGATGGATGGAT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 149 AN: 125568 Hom.: 1 Cov.: 26

Gnomad AFR AF: 0.00330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000549

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000394

Gnomad MID AF: 0.00485

Gnomad NFE AF: 0.000432

Gnomad OTH AF: 0.00114

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

GnomAD4 genome AF: 0.00119 AC: 150 AN: 125694 Hom.: 1 Cov.: 26 AF XY: 0.00102 AC XY: 62 AN XY: 60778

African (AFR) AF: 0.00335 AC: 108 AN: 32250

American (AMR) AF: 0.000548 AC: 7 AN: 12766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3218

East Asian (EAS) AF: 0.00111 AC: 4 AN: 3602

South Asian (SAS) AF: 0.00 AC: 0 AN: 3318

European-Finnish (FIN) AF: 0.000394 AC: 3 AN: 7616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 194

European-Non Finnish (NFE) AF: 0.000432 AC: 26 AN: 60174

Other (OTH) AF: 0.00112 AC: 2 AN: 1786

Alfa AF: 0.0000623 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs111504264; hg19: chr20-45353445;