7-76390265-C-G

Variant names:

• chr7-76390265-C-G
• rs775089702
• NM_080744.2:c.1522G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080744.2(SSC4D):​c.1522G>C​(p.Gly508Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G508S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07406345).

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.1522G>C	p.Gly508Arg	missense	Exon 11 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.1522G>C	p.Gly508Arg	missense	Exon 11 of 11	ENSP00000275560.3	Q8WTU2-1
	SSC4D	ENST00000938541.1		c.1486G>C	p.Gly496Arg	missense	Exon 10 of 10	ENSP00000608600.1
	SSC4D	ENST00000938545.1		c.1303G>C	p.Gly435Arg	missense	Exon 11 of 11	ENSP00000608604.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461612 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111904

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.71
DANN	Benign	0.73
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.79	N
PhyloP100		-1.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.070
Sift	Benign	0.42	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.098
MutPred		0.47		Gain of MoRF binding (P = 0.0168)
MVP		0.092
MPC		0.69
ClinPred		0.066	T
GERP RS		-8.1
Varity_R		0.061
gMVP		0.41
Mutation Taster		=100/0	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: rs775089702; hg19: chr7-76019582;