7-76390253-G-C

Variant names:

• chr7-76390253-G-C
• rs773391280
• NM_080744.2:c.1534C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_080744.2(SSC4D):​c.1534C>G​(p.Arg512Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC4D	NM_080744.2	c.1534C>G	p.Arg512Gly	missense_variant	Exon 11 of 11	ENST00000275560.4	NP_542782.1
SSC4D	XM_024446664.2	c.1621C>G	p.Arg541Gly	missense_variant	Exon 12 of 12		XP_024302432.1
SSC4D	XM_017011750.2	c.1027C>G	p.Arg343Gly	missense_variant	Exon 8 of 8		XP_016867239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSC4D	ENST00000275560.4	c.1534C>G	p.Arg512Gly	missense_variant	Exon 11 of 11	1	NM_080744.2	ENSP00000275560.3
SSC4D	ENST00000492979.2	n.305C>G		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461644 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727146

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.75		Loss of solvent accessibility (P = 0.1077);
MVP		0.57
MPC		1.6
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.78
gMVP		0.58

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: rs773391280; hg19: chr7-76019570;