19-55489455-C-T

Variant names:

• chr19-55489455-C-T
• rs1198611541
• NM_001144950.2:c.154C>T

Variant summary

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

The NM_001144950.2(SSC5D):​c.154C>T​(p.Arg52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000452 in 1,328,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.07

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC5D	NM_001144950.2	c.154C>T	p.Arg52Cys	missense_variant	Exon 3 of 14	ENST00000389623.11	NP_001138422.1
SSC5D	NM_001195267.2	c.154C>T	p.Arg52Cys	missense_variant	Exon 3 of 13		NP_001182196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSC5D	ENST00000389623.11	c.154C>T	p.Arg52Cys	missense_variant	Exon 3 of 14	1	NM_001144950.2	ENSP00000374274.4
SSC5D	ENST00000587166.5	c.154C>T	p.Arg52Cys	missense_variant	Exon 3 of 13	1		ENSP00000467252.1
SSC5D	ENST00000594321.5	c.154C>T	p.Arg52Cys	missense_variant	Exon 3 of 3	4		ENSP00000470226.1
SSC5D	ENST00000588254.1	n.568C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000452 AC: 6 AN: 1328560 Hom.: 0 Cov.: 31 AF XY: 0.00000460 AC XY: 3 AN XY: 652464

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: 0.0000145

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000474

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.154C>T (p.R52C) alteration is located in exon 3 (coding exon 3) of the SSC5D gene. This alteration results from a C to T substitution at nucleotide position 154, causing the arginine (R) at amino acid position 52 to be replaced by a cysteine (C). 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	Pathogenic	0.66
BayesDel_addAF	Benign	0.0045	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T;.;T
Eigen	Benign	0.0097
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.3	.;M;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.1	.;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	.;.;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.37, 0.40
MutPred		0.68		Loss of solvent accessibility (P = 0.0199);Loss of solvent accessibility (P = 0.0199);Loss of solvent accessibility (P = 0.0199);
MVP		0.49
MPC		0.11
ClinPred		0.97	D
GERP RS		2.9
Varity_R		0.18
gMVP		0.43

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: rs1198611541; hg19: chr19-56000822;