6-152722222-A-T

Variant names:

• chr6-152722222-A-T
• NM_025107.3:c.677A>T

Variant summary

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

The NM_025107.3(MYCT1):​c.677A>T​(p.Glu226Val) 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: 32)
• Consequence: MYCT1 NM_025107.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.31
• Publications: 0 publications found

Genes affected

MYCT1 (HGNC:23172): (MYC target 1) Predicted to act upstream of or within hematopoietic stem cell homeostasis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025107.3. 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
	MYCT1	NM_025107.3	MANE Select	c.677A>T	p.Glu226Val	missense	Exon 2 of 2	NP_079383.2	Q8N699
	MYCT1	NM_001371624.1		c.533A>T	p.Glu178Val	missense	Exon 2 of 3	NP_001358553.1	D6Q1S4
	MYCT1	NM_001371625.1		c.533A>T	p.Glu178Val	missense	Exon 2 of 3	NP_001358554.1	D6Q1S4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCT1	ENST00000367245.6	TSL:1 MANE Select	c.677A>T	p.Glu226Val	missense	Exon 2 of 2	ENSP00000356214.5	Q8N699
	MYCT1	ENST00000532295.1	TSL:3	c.617A>T	p.Glu206Val	missense	Exon 2 of 3	ENSP00000434396.1	H0YDV5
	MYCT1	ENST00000529453.1	TSL:3	c.197-541A>T		intron	N/A	ENSP00000432612.1	E9PQ55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		8.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.97	D
Vest4		0.57
MutPred		0.31		Loss of disorder (P = 0.044)
MVP		0.28
MPC		0.059
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.50
gMVP		0.66
Mutation Taster		=38/62	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: chr6-153043357;