7-76395259-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080744.2(SSC4D):​c.940C>T​(p.Pro314Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,838 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 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.777
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017604083).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.940C>T p.Pro314Ser missense_variant Exon 7 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1027C>T p.Pro343Ser missense_variant Exon 8 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.433C>T p.Pro145Ser 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.940C>T p.Pro314Ser missense_variant Exon 7 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1

Frequencies

GnomAD3 genomes
AF:
0.000276
AC:
42
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000989
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251392
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.000861
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461524
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727050
show subpopulations
Gnomad4 AFR exome
AF:
0.00128
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:
0.0000166
GnomAD4 genome
AF:
0.000282
AC:
43
AN:
152314
Hom.:
0
Cov.:
32
AF XY:
0.000309
AC XY:
23
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00101
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000464
Hom.:
0
Bravo
AF:
0.000302
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.940C>T (p.P314S) 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 940, causing the proline (P) at amino acid position 314 to be replaced by a serine (S). 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
0.074
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
7.5
DANN
Benign
0.68
DEOGEN2
Benign
0.086
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.073
Sift
Benign
0.29
T
Sift4G
Benign
0.60
T
Polyphen
0.0020
B
Vest4
0.30
MVP
0.16
MPC
0.58
ClinPred
0.018
T
GERP RS
2.2
Varity_R
0.032
gMVP
0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148308343; hg19: chr7-76024576; API