19-55518207-C-T

Position:

• chr19-55518207-C-T

Variant summary

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

The NM_001144950.2(SSC5D):​c.3931C>T​(p.Pro1311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,314,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: SSC5D NM_001144950.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085893184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSC5D	NM_001144950.2	c.3931C>T	p.Pro1311Ser	missense_variant	14/14	ENST00000389623.11	NP_001138422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSC5D	ENST00000389623.11	c.3931C>T	p.Pro1311Ser	missense_variant	14/14	1	NM_001144950.2	ENSP00000374274.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000694 AC: 1 AN: 143996 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76708

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000443

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 7.61e-7 AC: 1 AN: 1314340 Hom.: 0 Cov.: 74 AF XY: 0.00 AC XY: 0 AN XY: 647794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000334

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.3
DANN	Benign	0.95
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.040	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.056
Sift	Benign	0.034	D
Sift4G	Benign	0.068	T
Polyphen		0.60	P
Vest4		0.071
MutPred		0.26		Gain of phosphorylation at P1311 (P = 0.0103);
MVP		0.048
MPC		0.014
ClinPred		0.080	T
GERP RS		2.5
Varity_R		0.025
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs778514407; hg19: chr19-56029574;