Variant 19-55489455-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07

Variant links:

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 links:

SSC5D (HGNC:):

SSC5D links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
SSC5D	NM_001144950.2 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	3/14	ENST00000389623.11	NP_001138422.1	A1L4H1-1
SSC5D	NM_001195267.2 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	3/13		NP_001182196.1	A1L4H1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SSC5D	ENST00000389623.11 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	3/14	1	NM_001144950.2	ENSP00000374274.4	A1L4H1-1
SSC5D	ENST00000587166.5 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	3/13	1		ENSP00000467252.1	A1L4H1-2
SSC5D	ENST00000594321.5 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	3/3	4		ENSP00000470226.1	M0QZ17
SSC5D	ENST00000588254.1 linkuse as main transcript	n.568C>T		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000452

AC:

AN:

1328560

Hom.:

Cov.:

AF XY:

0.00000460

AC XY:

AN XY:

652464

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

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

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

T;.;T

Eigen

Benign

0.0097

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.75

T;T;T

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.3

.;M;M

PrimateAI

Pathogenic

0.85

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over