11-45649837-G-T

Variant names:

• chr11-45649837-G-T
• NM_003654.6:c.1087C>A

Variant summary

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

The NM_003654.6(CHST1):​c.1087C>A​(p.Arg363Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHST1 NM_003654.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88

Genes affected

CHST1 (HGNC:1969): (carbohydrate sulfotransferase 1) This locus encodes a member of the keratin sulfotransferase family of proteins. The encoded enzyme catalyzes the sulfation of the proteoglycan keratin. [provided by RefSeq, Aug 2011]

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=0.28611127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST1	NM_003654.6	c.1087C>A	p.Arg363Ser	missense_variant	Exon 4 of 4	ENST00000308064.7	NP_003645.1
CHST1	XM_006718356.5	c.1087C>A	p.Arg363Ser	missense_variant	Exon 4 of 5		XP_006718419.1
CHST1	XM_017018459.3	c.1087C>A	p.Arg363Ser	missense_variant	Exon 4 of 5		XP_016873948.1
CHST1	XM_047427781.1	c.1087C>A	p.Arg363Ser	missense_variant	Exon 4 of 4		XP_047283737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST1	ENST00000308064.7	c.1087C>A	p.Arg363Ser	missense_variant	Exon 4 of 4	1	NM_003654.6	ENSP00000309270.2
CHST1	ENST00000533673.1	n.-203C>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459100 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726018

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1087C>A (p.R363S) alteration is located in exon 1 (coding exon 1) of the CHST1 gene. This alteration results from a C to A substitution at nucleotide position 1087, causing the arginine (R) at amino acid position 363 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.081
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.41	T
PrimateAI	Benign	0.48	T
PROVEAN	Benign	1.7	N
REVEL	Uncertain	0.38
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.84	P
Vest4		0.20
MutPred		0.57		Loss of MoRF binding (P = 0.0099);
MVP		0.56
MPC		1.8
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.14
gMVP		0.81

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: chr11-45671387;