Variant 7-76393528-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_080744.2(SSC4D):c.1210G>T(p.Gly404Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 1,372,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.80

Variant links:

Genes affected

SSC4D (HGNC:14461): (scavenger receptor cysteine rich family member with 4 domains) The scavenger receptor cysteine-rich (SRCR) superfamily is an ancient and highly conserved group of cell surface and/or secreted proteins, some of which are involved in the development of the immune system and the regulation of both innate and adaptive immune responses. Group B SRCR domains usually contain 8 regularly spaced cysteines that give rise to a well-defined intradomain disulfide-bond pattern.[supplied by OMIM, Apr 2004]

SSC4D links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC4D	NM_080744.2 link	c.1210G>T	p.Gly404Cys	missense_variant	Exon 9 of 11	ENST00000275560.4	NP_542782.1	Q8WTU2-1
SSC4D	XM_024446664.2 link	c.1297G>T	p.Gly433Cys	missense_variant	Exon 10 of 12		XP_024302432.1
SSC4D	XM_017011750.2 link	c.703G>T	p.Gly235Cys	missense_variant	Exon 6 of 8		XP_016867239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSC4D	ENST00000275560.4 link	c.1210G>T	p.Gly404Cys	missense_variant	Exon 9 of 11	1	NM_080744.2	ENSP00000275560.3		Q8WTU2-1
SSC4D	ENST00000492979.2 link	n.-38G>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000219

AC:

AN:

1372282

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

677680

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000523

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000291

AC:

AN:

3454

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1210G>T (p.G404C) alteration is located in exon 9 (coding exon 8) of the SSC4D gene. This alteration results from a G to T substitution at nucleotide position 1210, causing the glycine (G) at amino acid position 404 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

0.96

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.79

MutationAssessor

Pathogenic

4.5

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-7.0

REVEL

Pathogenic

0.74

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.89

MutPred

0.81

Loss of methylation at R403 (P = 0.046);

MVP

0.83

MPC

1.6

ClinPred

1.0

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.90

gMVP

0.75

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over