chr19-55489485-G-A

Position:

• chr19-55489485-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001144950.2(SSC5D):​c.184G>A​(p.Gly62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000951 in 1,472,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000095 (0 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.75

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSC5D	NM_001144950.2	c.184G>A	p.Gly62Ser	missense_variant	3/14	ENST00000389623.11	NP_001138422.1
SSC5D	NM_001195267.2	c.184G>A	p.Gly62Ser	missense_variant	3/13		NP_001182196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSC5D	ENST00000389623.11	c.184G>A	p.Gly62Ser	missense_variant	3/14	1	NM_001144950.2	ENSP00000374274.4
SSC5D	ENST00000587166.5	c.184G>A	p.Gly62Ser	missense_variant	3/13	1		ENSP00000467252.1
SSC5D	ENST00000594321.5	c.184G>A	p.Gly62Ser	missense_variant	3/3	4		ENSP00000470226.1
SSC5D	ENST00000588254.1	n.598G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000188 AC: 14 AN: 74648 Hom.: 0 AF XY: 0.000200 AC XY: 8 AN XY: 39992

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000706

Gnomad ASJ exome AF: 0.000324

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000368

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000209

Gnomad OTH exome AF: 0.000845

GnomAD4 exome AF: 0.0000954 AC: 126 AN: 1320430 Hom.: 0 Cov.: 31 AF XY: 0.000102 AC XY: 66 AN XY: 647038

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000411

Gnomad4 ASJ exome AF: 0.000292

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000264

Gnomad4 FIN exome AF: 0.0000295

Gnomad4 NFE exome AF: 0.0000847

Gnomad4 OTH exome AF: 0.000164

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6 AN XY: 74496

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000909 AC: 6

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

Jan 10, 2023

The c.184G>A (p.G62S) 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 184, causing the glycine (G) at amino acid position 62 to be replaced by a serine (S). 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	0.25
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Uncertain	2.9	.;M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.8	.;.;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0060	.;.;D
Sift4G	Uncertain	0.028	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.50, 0.60
MutPred		0.94		Gain of glycosylation at G62 (P = 0.0434);Gain of glycosylation at G62 (P = 0.0434);Gain of glycosylation at G62 (P = 0.0434);
MVP		0.78
MPC		0.11
ClinPred		0.50	D
GERP RS		3.9
Varity_R		0.43
gMVP		0.57

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: rs558923564; hg19: chr19-56000852;