11-6621795-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003737.4(DCHS1):ā€‹c.9881C>Gā€‹(p.Thr3294Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000487 in 1,438,652 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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000049 ( 0 hom. )

Consequence

DCHS1
NM_003737.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37
Variant links:
Genes affected
DCHS1 (HGNC:13681): (dachsous cadherin-related 1) This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing. [provided by RefSeq, Jul 2008]
DCHS1-AS1 (HGNC:40650): (DCHS1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17943466).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCHS1NM_003737.4 linkc.9881C>G p.Thr3294Arg missense_variant Exon 21 of 21 ENST00000299441.5 NP_003728.1 Q96JQ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCHS1ENST00000299441.5 linkc.9881C>G p.Thr3294Arg missense_variant Exon 21 of 21 1 NM_003737.4 ENSP00000299441.3 Q96JQ0
DCHS1-AS1ENST00000526456.1 linkn.345G>C non_coding_transcript_exon_variant Exon 1 of 2 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000475
AC:
1
AN:
210348
Hom.:
0
AF XY:
0.00000881
AC XY:
1
AN XY:
113522
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:
0.0000108
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000487
AC:
7
AN:
1438652
Hom.:
0
Cov.:
30
AF XY:
0.00000561
AC XY:
4
AN XY:
713272
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:
0.00
Gnomad4 NFE exome
AF:
0.00000545
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000319
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Aug 29, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 3294 of the DCHS1 protein (p.Thr3294Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DCHS1-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt DCHS1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.12
Sift
Benign
0.060
T
Sift4G
Uncertain
0.035
D
Polyphen
0.63
P
Vest4
0.38
MutPred
0.11
Loss of phosphorylation at T3294 (P = 0.0146);
MVP
0.53
MPC
0.29
ClinPred
0.62
D
GERP RS
4.9
Varity_R
0.14
gMVP
0.55

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: rs761356492; hg19: chr11-6643026; API