Variant 19-55489389-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001144950.2(SSC5D):c.88G>A(p.Ala30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,481,554 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 1 hom. )

Consequence

SSC5D
NM_001144950.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.767

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3154507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSC5D	NM_001144950.2 linkuse as main transcript	c.88G>A	p.Ala30Thr	missense_variant	3/14	ENST00000389623.11	NP_001138422.1	A1L4H1-1
SSC5D	NM_001195267.2 linkuse as main transcript	c.88G>A	p.Ala30Thr	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.88G>A	p.Ala30Thr	missense_variant	3/14	1	NM_001144950.2	ENSP00000374274.4	A1L4H1-1
SSC5D	ENST00000587166.5 linkuse as main transcript	c.88G>A	p.Ala30Thr	missense_variant	3/13	1		ENSP00000467252.1	A1L4H1-2
SSC5D	ENST00000594321.5 linkuse as main transcript	c.88G>A	p.Ala30Thr	missense_variant	3/3	4		ENSP00000470226.1	M0QZ17
SSC5D	ENST00000588254.1 linkuse as main transcript	n.502G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000278

AC:

AN:

1329190

Hom.:

Cov.:

AF XY:

0.0000337

AC XY:

AN XY:

653612

show subpopulations

Gnomad4 AFR exome

AF:

0.0000374

Gnomad4 AMR exome

AF:

0.0000415

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000275

Gnomad4 SAS exome

AF:

0.0000144

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000218

Gnomad4 OTH exome

AF:

0.0000363

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

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 31, 2024

The c.88G>A (p.A30T) 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 88, causing the alanine (A) at amino acid position 30 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

0.40

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;.;T

Eigen

Benign

0.10

Eigen_PC

Benign

-0.016

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

.;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.3

.;.;N

REVEL

Benign

0.20

Sift

Uncertain

0.023

.;.;D

Sift4G

Benign

0.069

T;T;T

Polyphen

0.99

.;.;D

Vest4

0.40, 0.39

MutPred

0.52

Loss of methylation at R32 (P = 0.1375);Loss of methylation at R32 (P = 0.1375);Loss of methylation at R32 (P = 0.1375);

MVP

0.43

MPC

0.11

ClinPred

0.17

GERP RS

4.2

Varity_R

0.17

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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