7-76391990-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080744.2(SSC4D):​c.1385G>T​(p.Arg462Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,442,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019173026).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.1385G>T p.Arg462Leu missense_variant Exon 10 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1472G>T p.Arg491Leu missense_variant Exon 11 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.878G>T p.Arg293Leu missense_variant Exon 7 of 8 XP_016867239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSC4DENST00000275560.4 linkc.1385G>T p.Arg462Leu missense_variant Exon 10 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1
SSC4DENST00000492979.2 linkn.156G>T non_coding_transcript_exon_variant Exon 2 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000603
AC:
13
AN:
215550
Hom.:
0
AF XY:
0.0000259
AC XY:
3
AN XY:
115950
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000422
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000125
AC:
18
AN:
1442074
Hom.:
1
Cov.:
31
AF XY:
0.00000419
AC XY:
3
AN XY:
715278
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000409
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:
0.0000168
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.0000331
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1385G>T (p.R462L) alteration is located in exon 10 (coding exon 9) of the SSC4D gene. This alteration results from a G to T substitution at nucleotide position 1385, causing the arginine (R) at amino acid position 462 to be replaced by a leucine (L). 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
0.083
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
8.2
DANN
Benign
0.94
DEOGEN2
Benign
0.055
T
Eigen
Benign
-0.99
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.34
N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.98
N
REVEL
Benign
0.039
Sift
Benign
0.34
T
Sift4G
Benign
0.32
T
Polyphen
0.035
B
Vest4
0.28
MutPred
0.34
Gain of relative solvent accessibility (P = 0.0522);
MVP
0.12
MPC
0.73
ClinPred
0.034
T
GERP RS
1.9
Varity_R
0.083
gMVP
0.33

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: rs758590531; hg19: chr7-76021307; API