7-76393675-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_080744.2(SSC4D):ā€‹c.1063G>Cā€‹(p.Gly355Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SSC4D
NM_080744.2 missense

Scores

12
5
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75
Variant links:
Genes affected
SSC4D (HGNC:14461): (scavenger receptor cysteine rich family member with 4 domains) The scavenger receptor cysteine-rich (SRCR) superfamily is an ancient and highly conserved group of cell surface and/or secreted proteins, some of which are involved in the development of the immune system and the regulation of both innate and adaptive immune responses. Group B SRCR domains usually contain 8 regularly spaced cysteines that give rise to a well-defined intradomain disulfide-bond pattern.[supplied by OMIM, Apr 2004]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.1063G>C p.Gly355Arg missense_variant Exon 9 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1150G>C p.Gly384Arg missense_variant Exon 10 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.556G>C p.Gly186Arg missense_variant Exon 6 of 8 XP_016867239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSC4DENST00000275560.4 linkc.1063G>C p.Gly355Arg missense_variant Exon 9 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1277884
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
627686
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
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
Nov 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1063G>C (p.G355R) alteration is located in exon 9 (coding exon 8) of the SSC4D gene. This alteration results from a G to C substitution at nucleotide position 1063, causing the glycine (G) at amino acid position 355 to be replaced by an arginine (R). 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
0.99
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.42
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Pathogenic
0.57
D
MetaRNN
Pathogenic
0.95
D
MetaSVM
Uncertain
0.79
D
MutationAssessor
Pathogenic
5.0
H
PrimateAI
Pathogenic
0.93
D
PROVEAN
Pathogenic
-5.8
D
REVEL
Pathogenic
0.80
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.014
D
Polyphen
0.49
P
Vest4
0.87
MutPred
0.84
Loss of catalytic residue at G355 (P = 0.0121);
MVP
0.71
MPC
1.3
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.80
gMVP
0.89

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.

Other links and lift over

dbSNP: rs1206313218; hg19: chr7-76022992; API