19-55489606-G-A

Position:

• chr19-55489606-G-A

Variant summary

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

The NM_001144950.2(SSC5D):​c.305G>A​(p.Arg102Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000726 in 1,377,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.181

Genes affected

SSC5D (HGNC:26641): (scavenger receptor cysteine rich family member with 5 domains) Predicted to enable fibronectin binding activity; laminin binding activity; and scavenger receptor activity. Predicted to be involved in defense response; detection of bacterial lipoprotein; and negative regulation of interleukin-8 production. Predicted to act upstream of or within regulation of interleukin-8 production. Predicted to be located in collagen-containing extracellular matrix. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SSC5D (HGNC:):

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=0.19540527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSC5D	NM_001144950.2	c.305G>A	p.Arg102Gln	missense_variant	3/14	ENST00000389623.11	NP_001138422.1
SSC5D	NM_001195267.2	c.305G>A	p.Arg102Gln	missense_variant	3/13		NP_001182196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSC5D	ENST00000389623.11	c.305G>A	p.Arg102Gln	missense_variant	3/14	1	NM_001144950.2	ENSP00000374274.4
SSC5D	ENST00000587166.5	c.305G>A	p.Arg102Gln	missense_variant	3/13	1		ENSP00000467252.1
SSC5D	ENST00000588254.1	n.719G>A		non_coding_transcript_exon_variant	2/5	2
SSC5D	ENST00000594321.5	c.*34G>A		downstream_gene_variant		4		ENSP00000470226.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000726 AC: 10 AN: 1377632 Hom.: 0 Cov.: 33 AF XY: 0.00000736 AC XY: 5 AN XY: 679370

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000287

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000558

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.305G>A (p.R102Q) alteration is located in exon 3 (coding exon 3) of the SSC5D gene. This alteration results from a G to A substitution at nucleotide position 305, causing the arginine (R) at amino acid position 102 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0027	.;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.083
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.16
Sift	Benign	0.077	.;T
Sift4G	Benign	0.33	T;T
Polyphen		1.0	.;D
Vest4		0.23
MutPred		0.65		Gain of ubiquitination at K105 (P = 0.0579);Gain of ubiquitination at K105 (P = 0.0579);
MVP		0.37
MPC		0.11
ClinPred		0.83	D
GERP RS		3.9
Varity_R		0.11
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-56000973;