7-76390066-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_080744.2(SSC4D):​c.1721C>T​(p.Pro574Leu) 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SSC4D
NM_080744.2 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046417177).
BP6
Variant 7-76390066-G-A is Benign according to our data. Variant chr7-76390066-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3170315.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.1721C>T p.Pro574Leu missense_variant Exon 11 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1808C>T p.Pro603Leu missense_variant Exon 12 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.1214C>T p.Pro405Leu missense_variant Exon 8 of 8 XP_016867239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSC4DENST00000275560.4 linkc.1721C>T p.Pro574Leu missense_variant Exon 11 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1
SSC4DENST00000492979.2 linkn.492C>T non_coding_transcript_exon_variant Exon 3 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 21, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
12
DANN
Benign
0.76
DEOGEN2
Benign
0.060
T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.046
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.023
Sift
Benign
0.18
T
Sift4G
Benign
0.23
T
Polyphen
0.0020
B
Vest4
0.091
MutPred
0.34
Gain of stability (P = 0.0076);
MVP
0.15
MPC
0.58
ClinPred
0.12
T
GERP RS
-0.56
Varity_R
0.035
gMVP
0.24

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.

Other links and lift over

hg19: chr7-76019383; API