7-76393585-C-T

Variant summary

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

The NM_080744.2(SSC4D):​c.1153G>A​(p.Ala385Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000516 in 1,510,818 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000055 ( 1 hom. )

Consequence

SSC4D
NM_080744.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.359
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=0.14298928).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SSC4DNM_080744.2 linkc.1153G>A p.Ala385Thr missense_variant Exon 9 of 11 ENST00000275560.4 NP_542782.1 Q8WTU2-1
SSC4DXM_024446664.2 linkc.1240G>A p.Ala414Thr missense_variant Exon 10 of 12 XP_024302432.1
SSC4DXM_017011750.2 linkc.646G>A p.Ala216Thr missense_variant Exon 6 of 8 XP_016867239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SSC4DENST00000275560.4 linkc.1153G>A p.Ala385Thr missense_variant Exon 9 of 11 1 NM_080744.2 ENSP00000275560.3 Q8WTU2-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152080
Hom.:
0
Cov.:
33
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:
0.000578
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:
0.0000280
AC:
3
AN:
107134
Hom.:
0
AF XY:
0.0000336
AC XY:
2
AN XY:
59566
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000411
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:
0.0000552
AC:
75
AN:
1358630
Hom.:
1
Cov.:
30
AF XY:
0.0000701
AC XY:
47
AN XY:
670270
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00224
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000352
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74416
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000362
AC:
3
Asia WGS
AF:
0.000582
AC:
2
AN:
3450

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1153G>A (p.A385T) alteration is located in exon 9 (coding exon 8) of the SSC4D gene. This alteration results from a G to A substitution at nucleotide position 1153, causing the alanine (A) at amino acid position 385 to be replaced by a threonine (T). 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
0.20
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.077
T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.23
N
LIST_S2
Uncertain
0.88
D
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.94
L
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.36
N
REVEL
Benign
0.092
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.20
B
Vest4
0.27
MutPred
0.65
Gain of phosphorylation at A385 (P = 0.0731);
MVP
0.19
MPC
0.74
ClinPred
0.27
T
GERP RS
3.8
Varity_R
0.15
gMVP
0.42

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: rs766590499; hg19: chr7-76022902; API