chr15-40471224-G-T

Variant names:

• chr15-40471224-G-T
• NM_130468.4:c.11G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_130468.4(CHST14):​c.11G>T​(p.Arg4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000838 in 1,193,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: CHST14 NM_130468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38692003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST14	NM_130468.4	c.11G>T	p.Arg4Leu	missense_variant	Exon 1 of 1	ENST00000306243.7	NP_569735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST14	ENST00000306243.7	c.11G>T	p.Arg4Leu	missense_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6
CHST14	ENST00000559991.1	c.11G>T	p.Arg4Leu	missense_variant	Exon 1 of 2	5		ENSP00000453882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.38e-7 AC: 1 AN: 1193870 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 583238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000414

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	Benign	0.12
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.61	T;T
M_CAP	Pathogenic	0.95	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.40	N;N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.29	T;T
Polyphen		0.99	D;.
Vest4		0.39
MutPred		0.18		Gain of catalytic residue at R4 (P = 0.0918);Gain of catalytic residue at R4 (P = 0.0918);
MVP		0.67
MPC		2.2
ClinPred		0.90	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.28
gMVP		0.66

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: chr15-40763423;