rs79849424

Variant names:

• chr20-46726190-C-G
• rs79849424
• NM_030777.4:c.1154C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-46726190-C-G
• chr20-46726190-C-T
• chr20-46726190-C-A

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.1154C>G​(p.Ala385Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,614,230 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A385V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.019 (93 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (228 hom.)
• Consequence: SLC2A10 NM_030777.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.0200
• Publications: 8 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024423003).
• BP6: Variant 20-46726190-C-G is Benign according to our data. Variant chr20-46726190-C-G is described in ClinVar as Benign. ClinVar VariationId is 139174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.055 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	NM_030777.4	MANE Select	c.1154C>G	p.Ala385Gly	missense	Exon 2 of 5	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.1154C>G	p.Ala385Gly	missense	Exon 2 of 5	ENSP00000352216.2	O95528
	SLC2A10	ENST00000862794.1		c.1448C>G	p.Ala483Gly	missense	Exon 2 of 5	ENSP00000532853.1
	SLC2A10	ENST00000862792.1		c.1154C>G	p.Ala385Gly	missense	Exon 2 of 6	ENSP00000532851.1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2824 AN: 152276 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00575

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.0114 AC: 2858 AN: 251270 AF XY: 0.0125

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.00413

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.00588 AC: 8594 AN: 1461836 Hom.: 228 Cov.: 33 AF XY: 0.00706 AC XY: 5135 AN XY: 727226

African (AFR) AF: 0.0568 AC: 1901 AN: 33478

American (AMR) AF: 0.00445 AC: 199 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0509 AC: 4387 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53370

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5768

European-Non Finnish (NFE) AF: 0.00141 AC: 1565 AN: 1112008

Other (OTH) AF: 0.00798 AC: 482 AN: 60394

GnomAD4 genome AF: 0.0186 AC: 2833 AN: 152394 Hom.: 93 Cov.: 33 AF XY: 0.0188 AC XY: 1400 AN XY: 74526

African (AFR) AF: 0.0569 AC: 2369 AN: 41598

American (AMR) AF: 0.00568 AC: 87 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0561 AC: 271 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 68038

Other (OTH) AF: 0.0123 AC: 26 AN: 2116

Alfa AF: 0.00571 Hom.: 5

Bravo AF: 0.0195

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0495 AC: 218

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0134 AC: 1626

Asia WGS AF: 0.0270 AC: 95 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00154

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Arterial tortuosity syndrome (5)
-	-	5	not specified (5)
-	-	2	Familial thoracic aortic aneurysm and aortic dissection (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.3
DANN	Benign	0.69
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.020
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.11
Sift	Benign	0.41	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.033
MPC		0.065
ClinPred		0.00097	T
GERP RS		-1.7
Varity_R		0.027
gMVP		0.36
Mutation Taster		=98/2	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: rs79849424; hg19: chr20-45354829;