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. Variant got 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. 14/21 in silico tools predict a benign 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: 0.0000014 (0 hom.)
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24241987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC4D	NM_080744.2	c.1447G>C	p.Glu483Gln	missense_variant	Exon 11 of 11	ENST00000275560.4	NP_542782.1
SSC4D	XM_024446664.2	c.1534G>C	p.Glu512Gln	missense_variant	Exon 12 of 12		XP_024302432.1
SSC4D	XM_017011750.2	c.940G>C	p.Glu314Gln	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.1447G>C	p.Glu483Gln	missense_variant	Exon 11 of 11	1	NM_080744.2	ENSP00000275560.3
SSC4D	ENST00000492979.2	n.218G>C		non_coding_transcript_exon_variant	Exon 3 of 3	5

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

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: 0.00000181

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	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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs749525908; hg19: chr7-76019657;