Variant 19-55489927-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001144950.2(SSC5D):c.407A>G(p.Asp136Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,398,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SSC5D
NM_001144950.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.462

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066801906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSC5D	NM_001144950.2 linkuse as main transcript	c.407A>G	p.Asp136Gly	missense_variant	4/14	ENST00000389623.11	NP_001138422.1	A1L4H1-1
SSC5D	NM_001195267.2 linkuse as main transcript	c.407A>G	p.Asp136Gly	missense_variant	4/13		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.407A>G	p.Asp136Gly	missense_variant	4/14	1	NM_001144950.2	ENSP00000374274.4	A1L4H1-1
SSC5D	ENST00000587166.5 linkuse as main transcript	c.407A>G	p.Asp136Gly	missense_variant	4/13	1		ENSP00000467252.1	A1L4H1-2
SSC5D	ENST00000588254.1 linkuse as main transcript	n.821A>G		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

155966

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

82690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000183

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:

0.0000100

AC:

AN:

1398250

Hom.:

Cov.:

AF XY:

0.00000870

AC XY:

AN XY:

689634

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000834

Gnomad4 OTH exome

AF:

0.0000345

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

Apr 18, 2023

The c.407A>G (p.D136G) alteration is located in exon 4 (coding exon 4) of the SSC5D gene. This alteration results from a A to G substitution at nucleotide position 407, causing the aspartic acid (D) at amino acid position 136 to be replaced by a glycine (G). 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

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

L;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.0070

Sift

Uncertain

0.023

.;D

Sift4G

Benign

0.23

T;D

Polyphen

0.0

.;B

Vest4

0.091

MutPred

0.33

Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);

MVP

0.014

MPC

0.015

ClinPred

0.031

GERP RS

-2.0

Varity_R

0.070

gMVP

0.55

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