Variant 7-76393465-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_080744.2(SSC4D):c.1273C>T(p.His425Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,382,176 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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 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=0.27852154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC4D	NM_080744.2 link	c.1273C>T	p.His425Tyr	missense_variant	Exon 9 of 11	ENST00000275560.4	NP_542782.1	Q8WTU2-1
SSC4D	XM_024446664.2 link	c.1360C>T	p.His454Tyr	missense_variant	Exon 10 of 12		XP_024302432.1
SSC4D	XM_017011750.2 link	c.766C>T	p.His256Tyr	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.1273C>T	p.His425Tyr	missense_variant	Exon 9 of 11	1	NM_080744.2	ENSP00000275560.3		Q8WTU2-1
SSC4D	ENST00000492979.2 link	n.26C>T		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000434

AC:

AN:

1382176

Hom.:

Cov.:

AF XY:

0.00000584

AC XY:

AN XY:

684946

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:

0.00000555

Gnomad4 OTH exome

AF:

0.00

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

Jun 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1273C>T (p.H425Y) alteration is located in exon 9 (coding exon 8) of the SSC4D gene. This alteration results from a C to T substitution at nucleotide position 1273, causing the histidine (H) at amino acid position 425 to be replaced by a tyrosine (Y). 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

0.62

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

Eigen

Benign

0.077

Eigen_PC

Benign

0.077

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.13

Sift

Uncertain

0.0020

Sift4G

Benign

0.13

Polyphen

0.75

Vest4

0.44

MutPred

0.47

Loss of disorder (P = 0.0985);

MVP

0.43

MPC

1.3

ClinPred

0.99

GERP RS

5.2

Varity_R

0.77

gMVP

0.42

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