Genetic Variant SUSD3:p.Thr55Ile (chr9-93075859-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_145006.4(SUSD3):c.164C>T(p.Thr55Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SUSD3
NM_145006.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUSD3	NM_145006.4 link	c.164C>T	p.Thr55Ile	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.164C>T	p.Thr55Ile	missense_variant	Exon 2 of 5	1	NM_145006.4	ENSP00000364621.3	Q96L08-1
SUSD3	ENST00000375469.5 link	c.125C>T	p.Thr42Ile	missense_variant	Exon 2 of 5	5		ENSP00000364618.1	Q96L08-2
SUSD3	ENST00000617293.4 link	c.164C>T	p.Thr55Ile	missense_variant	Exon 2 of 4	3		ENSP00000479555.1	A0A087WVN2
SUSD3	ENST00000465709.5 link	c.53-1987C>T		intron_variant	Intron 1 of 3	3		ENSP00000475051.1	S4R444

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251226

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73790

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.164C>T (p.T55I) 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 164, causing the threonine (T) at amino acid position 55 to be replaced by an isoleucine (I). 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

0.95

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;T;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.83

D;D;D

MetaSVM

Uncertain

-0.023

MutationAssessor

Uncertain

2.7

.;M;.

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-5.6

.;D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0020

.;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.94

MutPred

0.47

Loss of catalytic residue at T55 (P = 0.0741);Loss of catalytic residue at T55 (P = 0.0741);.;

MVP

0.61

MPC

1.3

ClinPred

0.98

GERP RS

5.3

Varity_R

0.57

gMVP

0.86

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