rs767895730

Variant names:

• chr6-152722204-C-G
• rs767895730
• NM_025107.3:c.659C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-152722204-C-G
• chr6-152722204-C-T

Variant summary

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

The NM_025107.3(MYCT1):​c.659C>G​(p.Pro220Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P220L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYCT1 NM_025107.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• 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.659C>G	p.Pro220Arg	missense	Exon 2 of 2	NP_079383.2	Q8N699
	MYCT1	NM_001371624.1		c.515C>G	p.Pro172Arg	missense	Exon 2 of 3	NP_001358553.1	D6Q1S4
	MYCT1	NM_001371625.1		c.515C>G	p.Pro172Arg	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.659C>G	p.Pro220Arg	missense	Exon 2 of 2	ENSP00000356214.5	Q8N699
	MYCT1	ENST00000532295.1	TSL:3	c.599C>G	p.Pro200Arg	missense	Exon 2 of 3	ENSP00000434396.1	H0YDV5
	MYCT1	ENST00000529453.1	TSL:3	c.197-559C>G		intron	N/A	ENSP00000432612.1	E9PQ55

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.14
Sift	Benign	0.057	T
Sift4G	Benign	0.26	T
Polyphen		0.99	D
Vest4		0.56
MutPred		0.24		Loss of glycosylation at P220 (P = 0.0135)
MVP		0.14
MPC		0.072
ClinPred		0.87	D
GERP RS		4.0
Varity_R		0.096
gMVP		0.27
Mutation Taster		=58/42	polymorphism

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

dbSNP: rs767895730; hg19: chr6-153043339;