Genetic Variant SSC5D:p.Ala115Val (chr19-55489645-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001144950.2(SSC5D):c.344C>T(p.Ala115Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,380,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. A115T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SSC5D
NM_001144950.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.241

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.374928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC5D	NM_001144950.2 link	c.344C>T	p.Ala115Val	missense_variant	Exon 3 of 14	ENST00000389623.11	NP_001138422.1	A1L4H1-1
SSC5D	NM_001195267.2 link	c.344C>T	p.Ala115Val	missense_variant	Exon 3 of 13		NP_001182196.1	A1L4H1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SSC5D	ENST00000389623.11 link	c.344C>T	p.Ala115Val	missense_variant	Exon 3 of 14	1	NM_001144950.2	ENSP00000374274.4	A1L4H1-1
SSC5D	ENST00000587166.5 link	c.344C>T	p.Ala115Val	missense_variant	Exon 3 of 13	1		ENSP00000467252.1	A1L4H1-2
SSC5D	ENST00000588254.1 link	n.758C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2
SSC5D	ENST00000594321.5 link	c.*73C>T		downstream_gene_variant		4		ENSP00000470226.1	M0QZ17

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000368

AC:

AN:

135878

Hom.:

AF XY:

0.0000682

AC XY:

AN XY:

73320

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000415

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000956

Gnomad SAS exome

AF:

0.0000896

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1380820

Hom.:

Cov.:

AF XY:

0.0000323

AC XY:

AN XY:

681178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000561

Gnomad4 SAS exome

AF:

0.0000507

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000269

Gnomad4 OTH exome

AF:

0.0000347

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.344C>T (p.A115V) 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 344, causing the alanine (A) at amino acid position 115 to be replaced by a valine (V). 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

0.40

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

-0.094

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;L

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.4

.;D

REVEL

Benign

0.21

Sift

Benign

0.14

.;T

Sift4G

Benign

0.065

T;T

Polyphen

1.0

.;D

Vest4

0.49

MutPred

0.72

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

MVP

0.14

MPC

0.11

ClinPred

0.40

GERP RS

3.9

Varity_R

0.17

gMVP

0.76

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