20-45335812-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002999.4(SDC4):​c.169G>A​(p.Asp57Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

SDC4
NM_002999.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57
Variant links:
Genes affected
SDC4 (HGNC:10661): (syndecan 4) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan that functions as a receptor in intracellular signaling. The encoded protein is found as a homodimer and is a member of the syndecan proteoglycan family. This gene is found on chromosome 20, while a pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41948777).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDC4NM_002999.4 linkc.169G>A p.Asp57Asn missense_variant Exon 2 of 5 ENST00000372733.3 NP_002990.2 P31431-1
SDC4XM_011528977.3 linkc.-17-2743G>A intron_variant Intron 1 of 3 XP_011527279.1 B4E1S6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SDC4ENST00000372733.3 linkc.169G>A p.Asp57Asn missense_variant Exon 2 of 5 1 NM_002999.4 ENSP00000361818.3 P31431-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152152
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251396
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135880
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:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000787
AC:
115
AN:
1461736
Hom.:
0
Cov.:
33
AF XY:
0.0000770
AC XY:
56
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000998
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152270
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74436
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000302
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.169G>A (p.D57N) alteration is located in exon 2 (coding exon 2) of the SDC4 gene. This alteration results from a G to A substitution at nucleotide position 169, causing the aspartic acid (D) at amino acid position 57 to be replaced by an asparagine (N). 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
0.12
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.47
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Pathogenic
2.9
M
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.11
Sift
Benign
0.28
T
Sift4G
Benign
0.73
T
Polyphen
1.0
D
Vest4
0.41
MVP
0.81
MPC
0.53
ClinPred
0.88
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.25
gMVP
0.43

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: rs200459038; hg19: chr20-43964452; API