11-45650274-C-T

Variant names:

• chr11-45650274-C-T
• NM_003654.6:c.650G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003654.6(CHST1):​c.650G>A​(p.Arg217His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHST1 NM_003654.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003654.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST1	NM_003654.6	MANE Select	c.650G>A	p.Arg217His	missense	Exon 4 of 4	NP_003645.1	O43916

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST1	ENST00000308064.7	TSL:1 MANE Select	c.650G>A	p.Arg217His	missense	Exon 4 of 4	ENSP00000309270.2	O43916
	CHST1	ENST00000891796.1		c.650G>A	p.Arg217His	missense	Exon 4 of 4	ENSP00000561855.1
	CHST1	ENST00000891797.1		c.650G>A	p.Arg217His	missense	Exon 4 of 4	ENSP00000561856.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.56	D
PhyloP100		6.1
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.42	N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.018	D
Sift4G	Benign	0.072	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.72		Loss of methylation at R217 (P = 0.0262)
MVP		0.84
MPC		2.3
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.11
gMVP		0.94
Mutation Taster		=46/54	disease causing

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

Other links and lift over

hg19: chr11-45671824; COSMIC: COSV57324844; COSMIC: COSV57324844;