chr15-40471244-G-A

Position:

• chr15-40471244-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: CHST14 NM_130468.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

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]

ACMG classification

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=0.12638512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST14	NM_130468.4	c.31G>A	p.Ala11Thr	missense_variant	1/1	ENST00000306243.7	NP_569735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST14	ENST00000306243.7	c.31G>A	p.Ala11Thr	missense_variant	1/1	6	NM_130468.4	ENSP00000307297.6
CHST14	ENST00000559991.1	c.31G>A	p.Ala11Thr	missense_variant	1/2	5		ENSP00000453882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000542 AC: 7 AN: 1292662 Hom.: 0 Cov.: 32 AF XY: 0.00000629 AC XY: 4 AN XY: 635608

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: 0.0000150

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000480

Gnomad4 OTH exome AF: 0.0000188

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Aug 27, 2024

BP4, PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.52	T;T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Pathogenic	0.86	D
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	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.081
gMVP		0.24

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

Other links and lift over

dbSNP: rs1447530551; hg19: chr15-40763443;