chr19-55489395-C-T

Variant names:

• chr19-55489395-C-T
• rs535910734
• NM_001144950.2:c.94C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001144950.2(SSC5D):​c.94C>T​(p.Arg32Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 1,484,344 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.230
• 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 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

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.94C>T	p.Arg32Cys	missense	Exon 3 of 14	NP_001138422.1	A1L4H1-1
	SSC5D	NM_001195267.2		c.94C>T	p.Arg32Cys	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.94C>T	p.Arg32Cys	missense	Exon 3 of 14	ENSP00000374274.4	A1L4H1-1
	SSC5D	ENST00000587166.5	TSL:1	c.94C>T	p.Arg32Cys	missense	Exon 3 of 13	ENSP00000467252.1	A1L4H1-2
	SSC5D	ENST00000594321.5	TSL:4	c.94C>T	p.Arg32Cys	missense	Exon 3 of 3	ENSP00000470226.1	M0QZ17

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000631 AC: 5 AN: 79280 AF XY: 0.0000229

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000140

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: 0.000838

GnomAD4 exome AF: 0.0000113 AC: 15 AN: 1332004 Hom.: 0 Cov.: 31 AF XY: 0.00000305 AC XY: 2 AN XY: 655426

African (AFR) AF: 0.00 AC: 0 AN: 26836

American (AMR) AF: 0.000286 AC: 7 AN: 24434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20998

East Asian (EAS) AF: 0.00 AC: 0 AN: 32764

South Asian (SAS) AF: 0.0000285 AC: 2 AN: 70268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4490

European-Non Finnish (NFE) AF: 0.00000379 AC: 4 AN: 1056492

Other (OTH) AF: 0.0000362 AC: 2 AN: 55264

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152340 Hom.: 1 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74498

African (AFR) AF: 0.0000481 AC: 2 AN: 41582

American (AMR) AF: 0.00137 AC: 21 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000314

ExAC AF: 0.0000227 AC: 2

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	0.93
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	4.8	H
PhyloP100		0.23
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.81		Loss of methylation at R32 (P = 0.0265)
MVP		0.60
MPC		0.11
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.73
gMVP		0.82
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs535910734; hg19: chr19-56000762;