chr15-101177783-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014918.5(CHSY1):c.2014A>G(p.Lys672Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CHSY1
NM_014918.5 missense
NM_014918.5 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.77
Genes affected
CHSY1 (HGNC:17198): (chondroitin sulfate synthase 1) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome. [provided by RefSeq, Dec 2011]
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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=0.10623601).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHSY1 | NM_014918.5 | c.2014A>G | p.Lys672Glu | missense_variant | 3/3 | ENST00000254190.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHSY1 | ENST00000254190.4 | c.2014A>G | p.Lys672Glu | missense_variant | 3/3 | 1 | NM_014918.5 | P1 | |
CHSY1 | ENST00000543813.2 | c.*1329A>G | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152240Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250948Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135710
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461892Hom.: 0 Cov.: 48 AF XY: 0.00000138 AC XY: 1AN XY: 727246
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74388
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2022 | The c.2014A>G (p.K672E) alteration is located in exon 3 (coding exon 3) of the CHSY1 gene. This alteration results from a A to G substitution at nucleotide position 2014, causing the lysine (K) at amino acid position 672 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of ubiquitination at K672 (P = 0.0161);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at