Variant 1-109336271-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000256637.8(SORT1):c.1340A>G(p.Glu447Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,613,092 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

SORT1
ENST00000256637.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

SORT1 (HGNC:11186): (sortilin 1) This gene encodes a member of the VPS10-related sortilin family of proteins. The encoded preproprotein is proteolytically processed by furin to generate the mature receptor. This receptor plays a role in the trafficking of different proteins to either the cell surface, or subcellular compartments such as lysosomes and endosomes. Expression levels of this gene may influence the risk of myocardial infarction in human patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

SORT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014367729).

BP6

Variant 1-109336271-T-C is Benign according to our data. Variant chr1-109336271-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638979.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SORT1	NM_002959.7 linkuse as main transcript	c.1340A>G	p.Glu447Gly	missense_variant	11/20	ENST00000256637.8	NP_002950.3
SORT1	NM_001205228.2 linkuse as main transcript	c.929A>G	p.Glu310Gly	missense_variant	11/20		NP_001192157.1
SORT1	XM_005271100.3 linkuse as main transcript	c.1337A>G	p.Glu446Gly	missense_variant	11/20		XP_005271157.1
SORT1	XM_005271101.4 linkuse as main transcript	c.932A>G	p.Glu311Gly	missense_variant	11/20		XP_005271158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SORT1	ENST00000256637.8 linkuse as main transcript	c.1340A>G	p.Glu447Gly	missense_variant	11/20	1	NM_002959.7	ENSP00000256637	P1	Q99523-1
SORT1	ENST00000538502.5 linkuse as main transcript	c.929A>G	p.Glu310Gly	missense_variant	11/20	2		ENSP00000438597		Q99523-2
SORT1	ENST00000466471.1 linkuse as main transcript	n.32A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00107

AC:

270

AN:

251400

Hom.:

AF XY:

0.00126

AC XY:

171

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00125

AC:

1829

AN:

1460762

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

956

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.000991

AC:

151

AN:

152330

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000945

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00108

AC:

131

EpiCase

AF:

0.000872

EpiControl

AF:

0.00184

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

SORT1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.085

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

.;N

MutationTaster

Benign

0.66

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.066

Sift

Benign

0.24

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.061

.;B

Vest4

0.17

MVP

0.17

MPC

0.29

ClinPred

0.021

GERP RS

5.7

Varity_R

0.18

gMVP

0.58

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

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