chr9-93075873-C-T

Variant summary

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

The NM_145006.4(SUSD3):​c.178C>T​(p.Arg60Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

SUSD3
NM_145006.4 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80
Variant links:
Genes affected
SUSD3 (HGNC:28391): (sushi domain containing 3) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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 rank MANE Protein UniProt
SUSD3NM_145006.4 linkc.178C>T p.Arg60Cys missense_variant Exon 2 of 5 ENST00000375472.8 NP_659443.1 Q96L08-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SUSD3ENST00000375472.8 linkc.178C>T p.Arg60Cys missense_variant Exon 2 of 5 1 NM_145006.4 ENSP00000364621.3 Q96L08-1
SUSD3ENST00000375469.5 linkc.139C>T p.Arg47Cys missense_variant Exon 2 of 5 5 ENSP00000364618.1 Q96L08-2
SUSD3ENST00000617293.4 linkc.178C>T p.Arg60Cys missense_variant Exon 2 of 4 3 ENSP00000479555.1 A0A087WVN2
SUSD3ENST00000465709.5 linkc.53-1973C>T intron_variant Intron 1 of 3 3 ENSP00000475051.1 S4R444

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152058
Hom.:
0
Cov.:
31
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251178
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135806
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000513
AC:
75
AN:
1461774
Hom.:
0
Cov.:
34
AF XY:
0.0000481
AC XY:
35
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152058
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74262
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.178C>T (p.R60C) 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 178, causing the arginine (R) at amino acid position 60 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
Benign
0.17
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.098
T;T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.063
D
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Benign
-0.57
T
MutationAssessor
Benign
0.90
.;L;.
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-3.1
.;D;D
REVEL
Benign
0.20
Sift
Uncertain
0.011
.;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
0.96, 0.96
.;D;P
Vest4
0.31
MVP
0.46
MPC
1.3
ClinPred
0.52
D
GERP RS
5.3
Varity_R
0.14
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs368292441; hg19: chr9-95838155; API