Genetic Variant CHST14:p.Ala11Thr (chr15-40471244-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130468.4(CHST14):c.31G>A(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000542 in 1,292,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000054 ( 0 hom. )

Consequence

CHST14
NM_130468.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96

Publications

0 publications found

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]

CHST14 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome, musculocontractural type 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Ehlers-Danlos syndrome, musculocontractural type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHST14 links:

ENSG00000302612 (HGNC:):

ENSG00000302612 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12638512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST14	NM_130468.4 link	c.31G>A	p.Ala11Thr	missense_variant	Exon 1 of 1	ENST00000306243.7	NP_569735.1	Q8NCH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHST14	ENST00000306243.7 link	c.31G>A	p.Ala11Thr	missense_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6	Q8NCH0
CHST14	ENST00000559991.1 link	c.31G>A	p.Ala11Thr	missense_variant	Exon 1 of 2	5		ENSP00000453882.1	H0YN65
ENSG00000302612	ENST00000788112.1 link	n.151+411C>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000542

AC:

AN:

1292662

Hom.:

Cov.:

AF XY:

0.00000629

AC XY:

AN XY:

635608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25138

American (AMR)

AF:

0.00

AC:

AN:

19594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20478

East Asian (EAS)

AF:

0.00

AC:

AN:

30018

South Asian (SAS)

AF:

0.0000150

AC:

AN:

66712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3790

European-Non Finnish (NFE)

AF:

0.00000480

AC:

AN:

1040956

Other (OTH)

AF:

0.0000188

AC:

AN:

53332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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 27, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BP4, PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.52

T;T

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.34

N;.

PhyloP100

2.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.26

T;T

Polyphen

0.041

B;.

Vest4

0.10

MutPred

0.11

Gain of phosphorylation at A11 (P = 0.0103);Gain of phosphorylation at A11 (P = 0.0103);

MVP

0.34

MPC

0.90

ClinPred

0.17

GERP RS

2.9

PromoterAI

-0.21

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.081

gMVP

0.24

Mutation Taster

=90/10

polymorphism

(source)

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

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chr15-40471244-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over