4-10021271-C-T

Position:

• chr4-10021271-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020041.3(SLC2A9):​c.150+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 1,612,978 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (11 hom.)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.15

Genes affected

SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-10021271-C-T is Benign according to our data. Variant chr4-10021271-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 347005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00215 (328/152362) while in subpopulation SAS AF= 0.00331 (16/4828). AF 95% confidence interval is 0.0029. There are 0 homozygotes in gnomad4. There are 165 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.150+9G>A		intron_variant		ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.150+9G>A		intron_variant		1	NM_020041.3	ENSP00000264784	A2

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 326 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00278 AC: 695 AN: 250198 Hom.: 2 AF XY: 0.00307 AC XY: 416 AN XY: 135330

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00261

Gnomad FIN exome AF: 0.00397

Gnomad NFE exome AF: 0.00377

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00303 AC: 4431 AN: 1460616 Hom.: 11 Cov.: 31 AF XY: 0.00310 AC XY: 2256 AN XY: 726640

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00217

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00268

Gnomad4 FIN exome AF: 0.00373

Gnomad4 NFE exome AF: 0.00329

Gnomad4 OTH exome AF: 0.00284

GnomAD4 genome AF: 0.00215 AC: 328 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.00221 AC XY: 165 AN XY: 74512

Gnomad4 AFR AF: 0.000625

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00325

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00261 Hom.: 0

Bravo AF: 0.00216

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00420

EpiControl AF: 0.00415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypouricemia, renal, 2 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 20, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs138627925; hg19: chr4-10022895; COSMIC: COSV53327077; COSMIC: COSV53327077;