rs749525908

Variant names:

• chr7-76390340-C-G
• rs749525908
• NM_080744.2:c.1447G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-76390340-C-G
• chr7-76390340-C-T

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.1447G>C​(p.Glu483Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. E483K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• 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=0.24241987).

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.1447G>C	p.Glu483Gln	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.1447G>C	p.Glu483Gln	missense	Exon 11 of 11	ENSP00000275560.3	Q8WTU2-1
	SSC4D	ENST00000938541.1		c.1411G>C	p.Glu471Gln	missense	Exon 10 of 10	ENSP00000608600.1
	SSC4D	ENST00000938545.1		c.1228G>C	p.Glu410Gln	missense	Exon 11 of 11	ENSP00000608604.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453288 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721984

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25424

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 85144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5538

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107174

Other (OTH) AF: 0.00 AC: 0 AN: 60002

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.065	T
Eigen	Benign	0.060
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.17
Sift	Benign	0.56	T
Sift4G	Benign	0.54	T
Polyphen		0.29	B
Vest4		0.23
MutPred		0.55		Gain of MoRF binding (P = 0.0179)
MVP		0.35
MPC		1.1
ClinPred		0.74	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.51
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749525908; hg19: chr7-76019657;