7-76395289-T-C

Variant names:

• chr7-76395289-T-C
• NM_080744.2:c.910A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080744.2(SSC4D):​c.910A>G​(p.Thr304Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: SSC4D NM_080744.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02

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]

ACMG classification

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=0.2751146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSC4D	NM_080744.2	c.910A>G	p.Thr304Ala	missense_variant	Exon 7 of 11	ENST00000275560.4	NP_542782.1
SSC4D	XM_024446664.2	c.997A>G	p.Thr333Ala	missense_variant	Exon 8 of 12		XP_024302432.1
SSC4D	XM_017011750.2	c.403A>G	p.Thr135Ala	missense_variant	Exon 4 of 8		XP_016867239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSC4D	ENST00000275560.4	c.910A>G	p.Thr304Ala	missense_variant	Exon 7 of 11	1	NM_080744.2	ENSP00000275560.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.910A>G (p.T304A) alteration is located in exon 7 (coding exon 6) of the SSC4D gene. This alteration results from a A to G substitution at nucleotide position 910, causing the threonine (T) at amino acid position 304 to be replaced by an alanine (A). 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	0.064
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.060
Sift	Benign	0.21	T
Sift4G	Benign	0.31	T
Polyphen		0.036	B
Vest4		0.60
MutPred		0.35		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.14
MPC		0.56
ClinPred		0.24	T
GERP RS		4.0
Varity_R		0.045
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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.

Other links and lift over

hg19: chr7-76024606;