rs377142129

Variant names:

• chr20-46709722-C-T
• rs377142129
• NM_030777.4:c.-15C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_030777.4(SLC2A10):​c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,545,498 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (5 hom.)
• Consequence: SLC2A10 NM_030777.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.0900
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 20-46709722-C-T is Benign according to our data. Variant chr20-46709722-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 139185.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00167 (255/152242) while in subpopulation AMR AF = 0.00287 (44/15306). AF 95% confidence interval is 0.0022. There are 2 homozygotes in GnomAd4. There are 115 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.-15C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_110404.1	O95528
	SLC2A10	NM_030777.4	MANE Select	c.-15C>T		5_prime_UTR	Exon 1 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.-15C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000352216.2	O95528
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.-15C>T		5_prime_UTR	Exon 1 of 5	ENSP00000352216.2	O95528
	SLC2A10	ENST00000862794.1		c.-15C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000532853.1

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 255 AN: 152130 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00243

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00135 AC: 184 AN: 136752 AF XY: 0.00135

Gnomad AFR exome AF: 0.000535

Gnomad AMR exome AF: 0.00224

Gnomad ASJ exome AF: 0.000125

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000659

Gnomad NFE exome AF: 0.00223

Gnomad OTH exome AF: 0.00273

GnomAD4 exome AF: 0.00182 AC: 2541 AN: 1393256 Hom.: 5 Cov.: 30 AF XY: 0.00177 AC XY: 1215 AN XY: 687248

African (AFR) AF: 0.000453 AC: 14 AN: 30894

American (AMR) AF: 0.00262 AC: 93 AN: 35564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25022

East Asian (EAS) AF: 0.00 AC: 0 AN: 35376

South Asian (SAS) AF: 0.000380 AC: 30 AN: 78878

European-Finnish (FIN) AF: 0.0000839 AC: 4 AN: 47688

Middle Eastern (MID) AF: 0.00813 AC: 37 AN: 4552

European-Non Finnish (NFE) AF: 0.00209 AC: 2248 AN: 1077574

Other (OTH) AF: 0.00199 AC: 115 AN: 57708

GnomAD4 genome AF: 0.00167 AC: 255 AN: 152242 Hom.: 2 Cov.: 33 AF XY: 0.00154 AC XY: 115 AN XY: 74442

African (AFR) AF: 0.000626 AC: 26 AN: 41548

American (AMR) AF: 0.00287 AC: 44 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 67988

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00154 Hom.: 0

Bravo AF: 0.00185

Asia WGS AF: 0.000579 AC: 2 AN: 3470

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	1	-	Arterial tortuosity syndrome (1)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.1
DANN	Benign	0.96
PhyloP100		-0.090
PromoterAI		-0.074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism

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: rs377142129; hg19: chr20-45338361;