rs193920914

Variant names:

• chr15-40955384-G-A
• rs193920914
• NM_024111.6:c.279G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-40955384-G-A
• chr15-40955384-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024111.6(CHAC1):​c.279G>A​(p.Trp93*) variant causes a stop gained change involving the alteration of a conserved nucleotide. 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 (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHAC1 NM_024111.6 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

CHAC1 (HGNC:28680): (ChaC glutathione specific gamma-glutamylcyclotransferase 1) This gene encodes a member of the gamma-glutamylcyclotransferase family of proteins. The encoded protein has been shown to promote neuronal differentiation by deglycination of the Notch receptor, which prevents receptor maturation and inhibits Notch signaling. This protein may also play a role in the unfolded protein response, and in regulation of glutathione levels and oxidative balance in the cell. Elevated expression of this gene may indicate increased risk of cancer recurrence among breast and ovarian cancer patients. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
CHAC1	NM_024111.6	c.279G>A	p.Trp93*	stop_gained	Exon 3 of 3	ENST00000617768.5	NP_077016.3
CHAC1	NM_001142776.4	c.279G>A	p.Trp93*	stop_gained	Exon 3 of 4		NP_001136248.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAC1	ENST00000617768.5	c.279G>A	p.Trp93*	stop_gained	Exon 3 of 3	1	NM_024111.6	ENSP00000484644.2
CHAC1	ENST00000444189.7	c.279G>A	p.Trp93*	stop_gained	Exon 3 of 4	1		ENSP00000395466.3
CHAC1	ENST00000487220.1	c.-277G>A		5_prime_UTR_variant	Exon 2 of 2	3		ENSP00000452707.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

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Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	42
DANN	Uncertain	0.98
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		10
Vest4		0.54
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs193920914; hg19: chr15-41247582; COSMIC: COSV71436230;