1-35111893-G-T

Variant names:

• chr1-35111893-G-T
• rs758501182
• NM_024772.5:c.1083G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Supporting PM2

The NM_001289091.2(ZMYM1):​c.3G>T​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZMYM1 NM_001289091.2 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• 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 3 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 68 codons. Genomic position: 35113112. Lost 0.086 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289091.2. 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.1083G>T	p.Met361Ile	missense	Exon 8 of 10	NP_079048.3
	ZMYM1	NM_001289091.2		c.3G>T	p.Met1?	start_lost	Exon 9 of 11	NP_001276020.1
	ZMYM1	NM_001289088.2		c.1083G>T	p.Met361Ile	missense	Exon 9 of 11	NP_001276017.1	Q5SVZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM1	ENST00000359858.9	TSL:1 MANE Select	c.1083G>T	p.Met361Ile	missense	Exon 8 of 10	ENSP00000352920.4	Q5SVZ6
	ZMYM1	ENST00000373330.1	TSL:1	c.1083G>T	p.Met361Ile	missense	Exon 9 of 11	ENSP00000362427.1	Q5SVZ6
	ZMYM1	ENST00000373329.5	TSL:1	n.1039G>T		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439354 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712390

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32776

American (AMR) AF: 0.00 AC: 0 AN: 42034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25658

East Asian (EAS) AF: 0.00 AC: 0 AN: 39190

South Asian (SAS) AF: 0.00 AC: 0 AN: 82604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1098840

Other (OTH) AF: 0.00 AC: 0 AN: 59396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.20
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.065
Sift	Benign	0.22	T
Sift4G	Benign	0.22	T
Polyphen		0.15	B
Vest4		0.23
MutPred		0.34		Gain of catalytic residue at L366 (P = 0.0488)
MVP		0.088
MPC		0.19
ClinPred		0.052	T
GERP RS		0.53
Varity_R		0.092
gMVP		0.099
Mutation Taster		=100/0	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: rs758501182; hg19: chr1-35577494;