6-152721813-T-C

Position:

• chr6-152721813-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025107.3(MYCT1):​c.268T>C​(p.Phe90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: MYCT1 NM_025107.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.134

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03980601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCT1	NM_025107.3	c.268T>C	p.Phe90Leu	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.268T>C	p.Phe90Leu	missense_variant	2/2	1	NM_025107.3	ENSP00000356214.5
MYCT1	ENST00000532295.1	c.208T>C	p.Phe70Leu	missense_variant	2/3	3		ENSP00000434396.1
MYCT1	ENST00000529453.1	c.197-950T>C		intron_variant		3		ENSP00000432612.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461878 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Mar 01, 2024

The c.268T>C (p.F90L) alteration is located in exon 2 (coding exon 2) of the MYCT1 gene. This alteration results from a T to C substitution at nucleotide position 268, causing the phenylalanine (F) at amino acid position 90 to be replaced by a leucine (L). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Benign	0.37
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.32	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.027
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.34		Gain of MoRF binding (P = 0.1138);
MVP		0.014
MPC		0.012
ClinPred		0.033	T
GERP RS		0.77
Varity_R		0.065
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs2099724753; hg19: chr6-153042948;