6-152722222-A-T

Position:

• chr6-152722222-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

MYCT1 (HGNC:):

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/exons	MANE	Protein	UniProt
MYCT1	NM_025107.3	c.677A>T	p.Glu226Val	missense_variant	2/2	ENST00000367245.6	NP_079383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYCT1	ENST00000367245.6	c.677A>T	p.Glu226Val	missense_variant	2/2	1	NM_025107.3	ENSP00000356214.5
MYCT1	ENST00000532295.1	c.617A>T	p.Glu206Val	missense_variant	2/3	3		ENSP00000434396.1
MYCT1	ENST00000529453.1	c.197-541A>T		intron_variant		3		ENSP00000432612.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.677A>T (p.E226V) alteration is located in exon 2 (coding exon 2) of the MYCT1 gene. This alteration results from a A to T substitution at nucleotide position 677, causing the glutamic acid (E) at amino acid position 226 to be replaced by a valine (V). 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	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
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

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: chr6-153043357;