7-76393443-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080744.2(SSC4D):ā€‹c.1295A>Gā€‹(p.Asn432Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000197 in 1,521,438 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000015 ( 0 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31474656).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.1295A>G p.Asn432Ser missense_variant Exon 9 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1382A>G p.Asn461Ser missense_variant Exon 10 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.788A>G p.Asn263Ser 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.1295A>G p.Asn432Ser missense_variant Exon 9 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1
SSC4DENST00000492979.2 linkn.48A>G non_coding_transcript_exon_variant Exon 1 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152044
Hom.:
0
Cov.:
33
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000668
AC:
1
AN:
149738
Hom.:
0
AF XY:
0.0000118
AC XY:
1
AN XY:
85078
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:
0.0000145
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000146
AC:
2
AN:
1369394
Hom.:
0
Cov.:
30
AF XY:
0.00000295
AC XY:
2
AN XY:
678552
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000186
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152044
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74270
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000169
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1295A>G (p.N432S) alteration is located in exon 9 (coding exon 8) of the SSC4D gene. This alteration results from a A to G substitution at nucleotide position 1295, causing the asparagine (N) at amino acid position 432 to be replaced by a serine (S). 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
0.43
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.096
T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.084
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.5
L
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-4.2
D
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.010
D
Polyphen
0.54
P
Vest4
0.33
MutPred
0.47
Gain of glycosylation at N432 (P = 0.0418);
MVP
0.50
MPC
0.65
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.87
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs757199415; hg19: chr7-76022760; API