7-76393677-C-G

Variant names:

• chr7-76393677-C-G
• NM_080744.2:c.1061G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.105

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]

ACMG classification

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
SSC4D	NM_080744.2	c.1061G>C	p.Arg354Pro	missense_variant	Exon 9 of 11	ENST00000275560.4	NP_542782.1
SSC4D	XM_024446664.2	c.1148G>C	p.Arg383Pro	missense_variant	Exon 10 of 12		XP_024302432.1
SSC4D	XM_017011750.2	c.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
SSC4D	ENST00000275560.4	c.1061G>C	p.Arg354Pro	missense_variant	Exon 9 of 11	1	NM_080744.2	ENSP00000275560.3
SSC4D	ENST00000492979.2	n.-187G>C		upstream_gene_variant		5

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

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;