7-76393850-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.1001C>T​(p.Ala334Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,604,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.438
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=0.0567542).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.1001C>T p.Ala334Val missense_variant Exon 8 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1088C>T p.Ala363Val missense_variant Exon 9 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.494C>T p.Ala165Val missense_variant Exon 5 of 8 XP_016867239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSC4DENST00000275560.4 linkc.1001C>T p.Ala334Val missense_variant Exon 8 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152212
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000699
AC:
16
AN:
228744
Hom.:
0
AF XY:
0.0000644
AC XY:
8
AN XY:
124286
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000312
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:
0.000146
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000158
AC:
230
AN:
1451882
Hom.:
1
Cov.:
34
AF XY:
0.000140
AC XY:
101
AN XY:
721356
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000457
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:
0.000205
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152212
Hom.:
0
Cov.:
31
AF XY:
0.000108
AC XY:
8
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000174
Hom.:
0
Bravo
AF:
0.000117
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000908
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1001C>T (p.A334V) alteration is located in exon 8 (coding exon 7) of the SSC4D gene. This alteration results from a C to T substitution at nucleotide position 1001, causing the alanine (A) at amino acid position 334 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
0.098
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.070
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.075
Sift
Benign
0.27
T
Sift4G
Benign
0.39
T
Polyphen
0.020
B
Vest4
0.064
MVP
0.15
MPC
0.57
ClinPred
0.082
T
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.093
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs368362406; hg19: chr7-76023167; API