NM_024772.5:c.305C>G

Variant names:

• chr1-35097452-C-G
• NM_024772.5:c.305C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024772.5(ZMYM1):​c.305C>G​(p.Ala102Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYM1 NM_024772.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.34
• Publications: 0 publications found

Genes affected

ZMYM1 (HGNC:26253): (zinc finger MYM-type containing 1) Predicted to enable protein dimerization activity and zinc ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024772.5. 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
	ZMYM1	NM_024772.5	MANE Select	c.305C>G	p.Ala102Gly	missense	Exon 4 of 10	NP_079048.3
	ZMYM1	NM_001289088.2		c.305C>G	p.Ala102Gly	missense	Exon 5 of 11	NP_001276017.1	Q5SVZ6
	ZMYM1	NM_001289090.2		c.305C>G	p.Ala102Gly	missense	Exon 5 of 11	NP_001276019.1	Q5SVZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM1	ENST00000359858.9	TSL:1 MANE Select	c.305C>G	p.Ala102Gly	missense	Exon 4 of 10	ENSP00000352920.4	Q5SVZ6
	ZMYM1	ENST00000373330.1	TSL:1	c.305C>G	p.Ala102Gly	missense	Exon 5 of 11	ENSP00000362427.1	Q5SVZ6
	ZMYM1	ENST00000373329.5	TSL:1	n.261C>G		non_coding_transcript_exon	Exon 3 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.84		Loss of sheet (P = 0.0817)
MVP		0.56
MPC		0.67
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.31
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-35563053;