1-35094043-G-T

Variant names:

• chr1-35094043-G-T
• rs373863327
• NM_024772.5:c.56G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024772.5(ZMYM1):​c.56G>T​(p.Gly19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. G19E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMYM1 NM_024772.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111278504).

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.56G>T	p.Gly19Val	missense	Exon 2 of 10	NP_079048.3
	ZMYM1	NM_001289088.2		c.56G>T	p.Gly19Val	missense	Exon 3 of 11	NP_001276017.1	Q5SVZ6
	ZMYM1	NM_001289090.2		c.56G>T	p.Gly19Val	missense	Exon 3 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.56G>T	p.Gly19Val	missense	Exon 2 of 10	ENSP00000352920.4	Q5SVZ6
	ZMYM1	ENST00000373330.1	TSL:1	c.56G>T	p.Gly19Val	missense	Exon 3 of 11	ENSP00000362427.1	Q5SVZ6
	ZMYM1	ENST00000373329.5	TSL:1	n.53-1776G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.059	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.19
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.073
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.041	D
Polyphen		0.34	B
Vest4		0.23
MutPred		0.23		Gain of helix (P = 0.0425)
MVP		0.15
MPC		0.26
ClinPred		0.67	D
GERP RS		-2.4
Varity_R		0.065
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs373863327; hg19: chr1-35559644;