Variant chr19-55489644-G-A 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.343G>A(p.Ala115Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000196 in 1,533,122 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SSC5D
NM_001144950.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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.343G>A	p.Ala115Thr	missense_variant	3/14	ENST00000389623.11	NP_001138422.1	A1L4H1-1
SSC5D	NM_001195267.2 linkuse as main transcript	c.343G>A	p.Ala115Thr	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.343G>A	p.Ala115Thr	missense_variant	3/14	1	NM_001144950.2	ENSP00000374274.4	A1L4H1-1
SSC5D	ENST00000587166.5 linkuse as main transcript	c.343G>A	p.Ala115Thr	missense_variant	3/13	1		ENSP00000467252.1	A1L4H1-2
SSC5D	ENST00000588254.1 linkuse as main transcript	n.757G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

136010

Hom.:

AF XY:

0.0000136

AC XY:

AN XY:

73390

show subpopulations

Gnomad AFR exome

AF:

0.000139

Gnomad AMR exome

AF:

0.00

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:

0.0000369

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000203

AC:

AN:

1380938

Hom.:

Cov.:

AF XY:

0.0000176

AC XY:

AN XY:

681234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000204

Gnomad4 OTH exome

AF:

0.0000693

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000403

AC:

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

Jan 30, 2024

The c.343G>A (p.A115T) 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 343, causing the alanine (A) at amino acid position 115 to be replaced by a threonine (T). 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

Uncertain

0.43

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

.;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Uncertain

-0.044

MutationAssessor

Pathogenic

3.7

H;H

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.6

.;D

REVEL

Benign

0.28

Sift

Uncertain

0.0090

.;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

.;D

Vest4

0.64

MutPred

0.74

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.24

MPC

0.11

ClinPred

0.94

GERP RS

3.9

Varity_R

0.28

gMVP

0.74

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

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