11-45650583-C-T

Variant names:

• chr11-45650583-C-T
• NM_003654.6:c.341G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003654.6(CHST1):​c.341G>A​(p.Arg114Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.90

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST1	NM_003654.6	c.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 4	ENST00000308064.7	NP_003645.1
CHST1	XM_006718356.5	c.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 5		XP_006718419.1
CHST1	XM_017018459.3	c.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 5		XP_016873948.1
CHST1	XM_047427781.1	c.341G>A	p.Arg114Gln	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.341G>A	p.Arg114Gln	missense_variant	Exon 4 of 4	1	NM_003654.6	ENSP00000309270.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.341G>A (p.R114Q) alteration is located in exon 1 (coding exon 1) of the CHST1 gene. This alteration results from a G to A substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a glutamine (Q). 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	Benign	0.13
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.14	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.60
Sift	Benign	0.068	T
Sift4G	Benign	0.36	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.47		Loss of helix (P = 0.0376);
MVP		0.79
MPC		2.3
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.22
gMVP		0.76

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: chr11-45672133; COSMIC: COSV100346179; COSMIC: COSV100346179;