Genetic Variant SUSD3:p.Arg47Cys (chr9-93075834-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145006.4(SUSD3):c.139C>T(p.Arg47Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,601,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R47H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SUSD3
NM_145006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

SUSD3 (HGNC:28391): (sushi domain containing 3) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SUSD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2605709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUSD3	NM_145006.4 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 2 of 5	ENST00000375472.8	NP_659443.1	Q96L08-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SUSD3	ENST00000375472.8 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 2 of 5	1	NM_145006.4	ENSP00000364621.3	Q96L08-1
SUSD3	ENST00000375469.5 link	c.100C>T	p.Arg34Cys	missense_variant	Exon 2 of 5	5		ENSP00000364618.1	Q96L08-2
SUSD3	ENST00000617293.4 link	c.139C>T	p.Arg47Cys	missense_variant	Exon 2 of 4	3		ENSP00000479555.1	A0A087WVN2
SUSD3	ENST00000465709.5 link	c.53-2012C>T		intron_variant	Intron 1 of 3	3		ENSP00000475051.1	S4R444

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149392

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

251004

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1451904

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722252

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000905

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149512

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72784

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000213

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.139C>T (p.R47C) alteration is located in exon 2 (coding exon 2) of the SUSD3 gene. This alteration results from a C to T substitution at nucleotide position 139, causing the arginine (R) at amino acid position 47 to be replaced by a cysteine (C). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.062

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-4.7

.;D;D

REVEL

Benign

0.036

Sift

Uncertain

0.0090

.;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.36, 0.31

.;B;B

Vest4

0.44

MutPred

0.36

Loss of MoRF binding (P = 0.0174);Loss of MoRF binding (P = 0.0174);.;

MVP

0.32

MPC

1.4

ClinPred

0.92

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.18

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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