7-76395291-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080744.2(SSC4D):​c.908C>T​(p.Ala303Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,808 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: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08499044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.908C>T p.Ala303Val missense_variant Exon 7 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.995C>T p.Ala332Val missense_variant Exon 8 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.401C>T p.Ala134Val missense_variant Exon 4 of 8 XP_016867239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSC4DENST00000275560.4 linkc.908C>T p.Ala303Val missense_variant Exon 7 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000597
AC:
15
AN:
251364
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000629
AC:
92
AN:
1461586
Hom.:
0
Cov.:
31
AF XY:
0.0000756
AC XY:
55
AN XY:
727074
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:
0.0000749
Gnomad4 NFE exome
AF:
0.0000746
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000133
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.908C>T (p.A303V) alteration is located in exon 7 (coding exon 6) of the SSC4D gene. This alteration results from a C to T substitution at nucleotide position 908, causing the alanine (A) at amino acid position 303 to be replaced by a valine (V). 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
0.088
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
16
DANN
Benign
0.67
DEOGEN2
Benign
0.063
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.085
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.40
N
REVEL
Benign
0.058
Sift
Benign
0.33
T
Sift4G
Benign
0.39
T
Polyphen
0.0010
B
Vest4
0.26
MVP
0.095
MPC
0.56
ClinPred
0.040
T
GERP RS
3.1
Varity_R
0.017
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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.

Other links and lift over

dbSNP: rs200977996; hg19: chr7-76024608; API