20-46729584-C-G

Variant names:

• chr20-46729584-C-G
• rs2425907
• NM_030777.4:c.1547+96C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030777.4(SLC2A10):​c.1547+96C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 1,314,908 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000069 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.113
• Publications: 6 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: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	NM_030777.4	MANE Select	c.1547+96C>G		intron	N/A	NP_110404.1	O95528

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.1547+96C>G		intron	N/A	ENSP00000352216.2	O95528
	SLC2A10	ENST00000862794.1		c.1841+96C>G		intron	N/A	ENSP00000532853.1
	SLC2A10	ENST00000862792.1		c.1679+96C>G		intron	N/A	ENSP00000532851.1

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145828 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000171 AC: 2 AN: 1169080 Hom.: 0 AF XY: 0.00000339 AC XY: 2 AN XY: 590174

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25796

American (AMR) AF: 0.00 AC: 0 AN: 40084

Ashkenazi Jewish (ASJ) AF: 0.0000455 AC: 1 AN: 21998

East Asian (EAS) AF: 0.00 AC: 0 AN: 34452

South Asian (SAS) AF: 0.00 AC: 0 AN: 79296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3838

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 875268

Other (OTH) AF: 0.0000207 AC: 1 AN: 48252

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145828 Hom.: 0 Cov.: 27 AF XY: 0.0000142 AC XY: 1 AN XY: 70512

African (AFR) AF: 0.0000255 AC: 1 AN: 39180

American (AMR) AF: 0.00 AC: 0 AN: 14564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 4888

South Asian (SAS) AF: 0.00 AC: 0 AN: 4542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67084

Other (OTH) AF: 0.00 AC: 0 AN: 1998

Alfa AF: 0.00 Hom.: 34211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.47
DANN	Benign	0.58
PhyloP100		0.11

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: rs2425907; hg19: chr20-45358223;