19-55489455-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144950.2. 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
	SSC5D	NM_001144950.2	MANE Select	c.154C>T	p.Arg52Cys	missense	Exon 3 of 14	NP_001138422.1	A1L4H1-1
	SSC5D	NM_001195267.2		c.154C>T	p.Arg52Cys	missense	Exon 3 of 13	NP_001182196.1	A1L4H1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSC5D	ENST00000389623.11	TSL:1 MANE Select	c.154C>T	p.Arg52Cys	missense	Exon 3 of 14	ENSP00000374274.4	A1L4H1-1
	SSC5D	ENST00000587166.5	TSL:1	c.154C>T	p.Arg52Cys	missense	Exon 3 of 13	ENSP00000467252.1	A1L4H1-2
	SSC5D	ENST00000594321.5	TSL:4	c.154C>T	p.Arg52Cys	missense	Exon 3 of 3	ENSP00000470226.1	M0QZ17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 74638 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 28074

American (AMR) AF: 0.00 AC: 0 AN: 24846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20824

East Asian (EAS) AF: 0.00 AC: 0 AN: 33986

South Asian (SAS) AF: 0.0000145 AC: 1 AN: 69092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4932

European-Non Finnish (NFE) AF: 0.00000474 AC: 5 AN: 1055610

Other (OTH) AF: 0.00 AC: 0 AN: 55184

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.0097
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-1.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.68		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
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: rs1198611541; hg19: chr19-56000822;