7-76393850-G-T

Variant names:

• chr7-76393850-G-T
• rs368362406
• NM_080744.2:c.1001C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080744.2(SSC4D):​c.1001C>A​(p.Ala334Asp) 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 1,451,882 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438

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=0.09298977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC4D	NM_080744.2	c.1001C>A	p.Ala334Asp	missense_variant	Exon 8 of 11	ENST00000275560.4	NP_542782.1
SSC4D	XM_024446664.2	c.1088C>A	p.Ala363Asp	missense_variant	Exon 9 of 12		XP_024302432.1
SSC4D	XM_017011750.2	c.494C>A	p.Ala165Asp	missense_variant	Exon 5 of 8		XP_016867239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSC4D	ENST00000275560.4	c.1001C>A	p.Ala334Asp	missense_variant	Exon 8 of 11	1	NM_080744.2	ENSP00000275560.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000437 AC: 1 AN: 228744 Hom.: 0 AF XY: 0.00000805 AC XY: 1 AN XY: 124286

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000973

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451882 Hom.: 0 Cov.: 34 AF XY: 0.00000277 AC XY: 2 AN XY: 721356

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.077
Sift	Benign	0.085	T
Sift4G	Benign	0.64	T
Polyphen		0.090	B
Vest4		0.096
MutPred		0.43		Gain of loop (P = 0.024);
MVP		0.18
MPC		0.88
ClinPred		0.20	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs368362406; hg19: chr7-76023167;