chr15-40472082-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_130468.4(CHST14):​c.869C>G​(p.Ala290Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A290V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CHST14
NM_130468.4 missense

Scores

14
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36
Variant links:
Genes affected
CHST14 (HGNC:24464): (carbohydrate sulfotransferase 14) This gene encodes a member of the HNK-1 family of sulfotransferases. The encoded protein transfers sulfate to the C-4 hydroxyl of N-acetylgalactosamine residues in dermatan sulfate. Mutations in this gene have been associated with adducted thumb-clubfoot syndrome.[provided by RefSeq, Mar 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 3 uncertain in NM_130468.4
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHST14NM_130468.4 linkc.869C>G p.Ala290Gly missense_variant Exon 1 of 1 ENST00000306243.7 NP_569735.1 Q8NCH0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHST14ENST00000306243.7 linkc.869C>G p.Ala290Gly missense_variant Exon 1 of 1 6 NM_130468.4 ENSP00000307297.6 Q8NCH0
CHST14ENST00000559991.1 linkc.794C>G p.Ala265Gly missense_variant Exon 2 of 2 5 ENSP00000453882.1 H0YN65

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461866
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.51
D;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.81
T;T
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.64
D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-2.7
D;N
REVEL
Uncertain
0.51
Sift
Benign
0.11
T;D
Sift4G
Benign
0.096
T;D
Polyphen
0.99
D;.
Vest4
0.53
MutPred
0.59
Gain of sheet (P = 0.0827);.;
MVP
0.81
MPC
2.0
ClinPred
0.97
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.57
gMVP
0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-40764281; API