dbSNP rs73487878: SLC3A2:p.Leu85Leu (chr11-62881276-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001013251.3(SLC3A2):c.253C>T(p.Leu85Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00384 in 1,589,912 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 93 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 95 hom. )

Consequence

SLC3A2
NM_001013251.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

SLC3A2 (HGNC:11026): (solute carrier family 3 member 2) This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

SLC3A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 11-62881276-C-T is Benign according to our data. Variant chr11-62881276-C-T is described in ClinVar as [Benign]. Clinvar id is 789624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC3A2	NM_001013251.3 link	c.253C>T	p.Leu85Leu	synonymous_variant	Exon 1 of 9	ENST00000338663.12	NP_001013269.1	P08195-2
SLC3A2	NM_001012662.3 link	c.559C>T	p.Leu187Leu	synonymous_variant	Exon 4 of 12		NP_001012680.1	P08195-5
SLC3A2	NM_002394.6 link	c.556C>T	p.Leu186Leu	synonymous_variant	Exon 4 of 12		NP_002385.3	P08195-1
SLC3A2	NM_001012664.3 link	c.370C>T	p.Leu124Leu	synonymous_variant	Exon 2 of 10		NP_001012682.1	P08195-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC3A2	ENST00000338663.12 link	c.253C>T	p.Leu85Leu	synonymous_variant	Exon 1 of 9	1	NM_001013251.3	ENSP00000340815.7		P08195-2

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2976

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00476

AC:

985

AN:

206764

Hom.:

AF XY:

0.00353

AC XY:

394

AN XY:

111552

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000749

Gnomad FIN exome

AF:

0.0000583

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.00325

GnomAD4 exome

AF:

0.00217

AC:

3125

AN:

1437540

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1320

AN XY:

712894

show subpopulations

Gnomad4 AFR exome

AF:

0.0765

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000843

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.00414

GnomAD4 genome

AF:

0.0195

AC:

2978

AN:

152372

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1413

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0671

Gnomad4 AMR

AF:

0.00777

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.00540

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over