NM_025107.3:c.299G>C

Variant names:

• chr6-152721844-G-C
• NM_025107.3:c.299G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025107.3(MYCT1):​c.299G>C​(p.Ser100Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYCT1 NM_025107.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.29
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35840234).

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.299G>C	p.Ser100Thr	missense	Exon 2 of 2	NP_079383.2	Q8N699
	MYCT1	NM_001371624.1		c.155G>C	p.Ser52Thr	missense	Exon 2 of 3	NP_001358553.1	D6Q1S4
	MYCT1	NM_001371625.1		c.155G>C	p.Ser52Thr	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.299G>C	p.Ser100Thr	missense	Exon 2 of 2	ENSP00000356214.5	Q8N699
	MYCT1	ENST00000532295.1	TSL:3	c.239G>C	p.Ser80Thr	missense	Exon 2 of 3	ENSP00000434396.1	H0YDV5
	MYCT1	ENST00000529453.1	TSL:3	c.197-919G>C		intron	N/A	ENSP00000432612.1	E9PQ55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

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	Benign	0.27
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.18
Sift	Benign	0.14	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.46		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.23
MPC		0.084
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.65
Mutation Taster		=29/71	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: chr6-153042979;