7-76393675-C-T

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_080744.2(SSC4D):​c.1063G>A​(p.Gly355Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,277,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC4D	NM_080744.2	c.1063G>A	p.Gly355Ser	missense_variant	Exon 9 of 11	ENST00000275560.4	NP_542782.1
SSC4D	XM_024446664.2	c.1150G>A	p.Gly384Ser	missense_variant	Exon 10 of 12		XP_024302432.1
SSC4D	XM_017011750.2	c.556G>A	p.Gly186Ser	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.1063G>A	p.Gly355Ser	missense_variant	Exon 9 of 11	1	NM_080744.2	ENSP00000275560.3
SSC4D	ENST00000492979.2	n.-185G>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000237 AC: 1 AN: 42112 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 24914

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: 0.000117

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000313 AC: 4 AN: 1277884 Hom.: 0 Cov.: 29 AF XY: 0.00000478 AC XY: 3 AN XY: 627686

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: 0.0000465

Gnomad4 FIN exome AF: 0.0000309

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.79
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	4.7	H
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.91		Loss of methylation at R356 (P = 0.0407);
MVP		0.65
MPC		1.4
ClinPred		0.90	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.76
gMVP		0.80

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

Other links and lift over

dbSNP: rs1206313218; hg19: chr7-76022992;