7-76393677-C-G

Variant summary

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

The NM_080744.2(SSC4D):​c.1061G>C​(p.Arg354Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SSC4D
NM_080744.2 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.105
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=0.37754792).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.1061G>C p.Arg354Pro missense_variant Exon 9 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1148G>C p.Arg383Pro missense_variant Exon 10 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.554G>C p.Arg185Pro 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.1061G>C p.Arg354Pro missense_variant Exon 9 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1061G>C (p.R354P) 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 1061, causing the arginine (R) at amino acid position 354 to be replaced by a proline (P). 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
0.70
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.078
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.69
T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.22
Sift
Uncertain
0.024
D
Sift4G
Benign
0.21
T
Polyphen
0.68
P
Vest4
0.47
MutPred
0.59
Loss of methylation at R354 (P = 0.0124);
MVP
0.25
MPC
1.5
ClinPred
0.78
D
GERP RS
2.5
Varity_R
0.48
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-76022994; API