chr7-76393675-C-G

Variant names:

• chr7-76393675-C-G
• rs1206313218
• NM_080744.2:c.1063G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_080744.2(SSC4D):​c.1063G>C​(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 (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.75
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080744.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC4D	NM_080744.2	MANE Select	c.1063G>C	p.Gly355Arg	missense	Exon 9 of 11	NP_542782.1	Q8WTU2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC4D	ENST00000275560.4	TSL:1 MANE Select	c.1063G>C	p.Gly355Arg	missense	Exon 9 of 11	ENSP00000275560.3	Q8WTU2-1
	SSC4D	ENST00000938541.1		c.1027G>C	p.Gly343Arg	missense	Exon 8 of 10	ENSP00000608600.1
	SSC4D	ENST00000938545.1		c.844G>C	p.Gly282Arg	missense	Exon 9 of 11	ENSP00000608604.1

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

African (AFR) AF: 0.00 AC: 0 AN: 25348

American (AMR) AF: 0.00 AC: 0 AN: 19270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19734

East Asian (EAS) AF: 0.00 AC: 0 AN: 28852

South Asian (SAS) AF: 0.00 AC: 0 AN: 64546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4900

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029934

Other (OTH) AF: 0.00 AC: 0 AN: 52906

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		7.7
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
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs1206313218; hg19: chr7-76022992;