Variant chr3-33153265-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015551.2(SUSD5):c.1367A>G(p.Glu456Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,613,920 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 9 hom. )

Consequence

SUSD5
NM_015551.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

Variant links:

Genes affected

SUSD5 (HGNC:29061): (sushi domain containing 5) Predicted to enable hyaluronic acid binding activity. Predicted to be involved in Notch signaling pathway. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUSD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054653585).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUSD5	NM_015551.2 link	c.1367A>G	p.Glu456Gly	missense_variant	5/5	ENST00000309558.8	NP_056366.1	O60279
SUSD5	XM_005265034.4 link	c.1178A>G	p.Glu393Gly	missense_variant	4/4		XP_005265091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUSD5	ENST00000309558.8 link	c.1367A>G	p.Glu456Gly	missense_variant	5/5	1	NM_015551.2	ENSP00000308727.3		O60279

Frequencies

GnomAD3 genomes

AF:

0.00203

AC:

308

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00278

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00160

AC:

399

AN:

249174

Hom.:

AF XY:

0.00160

AC XY:

216

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.000646

Gnomad AMR exome

AF:

0.00206

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00228

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00246

AC:

3591

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1735

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.000562

Gnomad4 NFE exome

AF:

0.00291

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152216

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00278

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00220

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000751

AC:

ESP6500EA

AF:

0.00323

AC:

ExAC

AF:

0.00155

AC:

188

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00255

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

Jan 18, 2022

The c.1367A>G (p.E456G) alteration is located in exon 5 (coding exon 5) of the SUSD5 gene. This alteration results from a A to G substitution at nucleotide position 1367, causing the glutamic acid (E) at amino acid position 456 to be replaced by a glycine (G). 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

Benign

0.090

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.49

M_CAP

Benign

0.0079

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.057

Sift

Uncertain

0.026

Sift4G

Benign

0.14

Polyphen

0.29

Vest4

0.085

MVP

0.35

MPC

0.053

ClinPred

0.020

GERP RS

4.5

Varity_R

0.10

gMVP

0.46

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