chr15-40471223-C-A

Variant names:

• chr15-40471223-C-A
• rs1272942478
• NM_130468.4:c.10C>A

Variant summary

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

The NM_130468.4(CHST14):​c.10C>A​(p.Arg4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHST14 NM_130468.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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=0.32555678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST14	NM_130468.4	c.10C>A	p.Arg4Ser	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.10C>A	p.Arg4Ser	missense_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6
CHST14	ENST00000559991.1	c.10C>A	p.Arg4Ser	missense_variant	Exon 1 of 2	5		ENSP00000453882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1256332 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 615110

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: 0.00

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	0.17
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.55	T;T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.17	N;N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.18	T;T
Polyphen		0.99	D;.
Vest4		0.14
MutPred		0.12		Gain of glycosylation at R4 (P = 0.0034);Gain of glycosylation at R4 (P = 0.0034);
MVP		0.70
MPC		2.1
ClinPred		0.88	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.19
gMVP		0.68

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: rs1272942478; hg19: chr15-40763422;