16-71536810-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001166395.2(CHST4):c.133G>A(p.Val45Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,531,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
CHST4
NM_001166395.2 missense
NM_001166395.2 missense
Scores
4
12
2
Clinical Significance
Conservation
PhyloP100: 3.88
Genes affected
CHST4 (HGNC:1972): (carbohydrate sulfotransferase 4) This gene encodes an N-acetylglucosamine 6-O sulfotransferase. The encoded enzyme transfers sulfate from 3'phosphoadenosine 5'phospho-sulfate to the 6-hydroxyl group of N-acetylglucosamine on glycoproteins. This protein is localized to the Golgi and is involved in the modification of glycan structures on ligands of the lymphocyte homing receptor L-selectin. Alternate splicing in the 5' UTR results in multiple transcript variants that encode the same protein. [provided by RefSeq, Oct 2009]
ZNF19 (HGNC:12981): (zinc finger protein 19) The protein encoded by this gene contains a zinc finger, a nucleic acid-binding domain present in many transcription factors. This gene is located in a region next to ZNF23, a gene also encoding a zinc finger protein, on chromosome 16. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHST4 | NM_001166395.2 | c.133G>A | p.Val45Met | missense_variant | 2/2 | ENST00000539698.4 | |
CHST4 | NM_005769.2 | c.133G>A | p.Val45Met | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHST4 | ENST00000539698.4 | c.133G>A | p.Val45Met | missense_variant | 2/2 | 1 | NM_001166395.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000371 AC: 7AN: 188428Hom.: 0 AF XY: 0.0000404 AC XY: 4AN XY: 99126
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GnomAD4 exome AF: 0.0000319 AC: 44AN: 1379596Hom.: 0 Cov.: 31 AF XY: 0.0000354 AC XY: 24AN XY: 677036
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74474
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2021 | The c.133G>A (p.V45M) alteration is located in exon 2 (coding exon 1) of the CHST4 gene. This alteration results from a G to A substitution at nucleotide position 133, causing the valine (V) at amino acid position 45 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0704);Gain of disorder (P = 0.0704);
MVP
MPC
ClinPred
D
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