Variant 9-113157757-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001860.3(SLC31A2):c.37C>T(p.Leu13Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,613,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SLC31A2
NM_001860.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.09

Variant links:

Genes affected

SLC31A2 (HGNC:11017): (solute carrier family 31 member 2) Predicted to enable copper ion transmembrane transporter activity. Predicted to be involved in cellular copper ion homeostasis. Predicted to act upstream of or within regulation of copper ion transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC31A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC31A2	NM_001860.3 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	2/4	ENST00000259392.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC31A2	ENST00000259392.8 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	2/4	1	NM_001860.3	P1
SLC31A2	ENST00000374220.3 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant, NMD_transcript_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000848

AC:

AN:

247732

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.0000650

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000125

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000110

AC:

161

AN:

1460950

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

102

AN XY:

726692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000990

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000131

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000483

AC:

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 03, 2022

The c.37C>T (p.L13F) alteration is located in exon 2 (coding exon 2) of the SLC31A2 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the leucine (L) at amino acid position 13 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Uncertain

0.020

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.41

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.23

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.58

Sift

Uncertain

0.010

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.66

MVP

0.59

MPC

0.77

ClinPred

0.39

GERP RS

5.9

Varity_R

0.37

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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