1-35111819-C-G

Variant names:

• chr1-35111819-C-G
• rs373549977
• NM_024772.5:c.1009C>G

Variant summary

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

The NM_001289091.2(ZMYM1):​c.-72C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,678 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 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18797183).

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.1009C>G	p.Pro337Ala	missense	Exon 8 of 10	NP_079048.3
	ZMYM1	NM_001289091.2		c.-72C>G		5_prime_UTR_premature_start_codon_gain	Exon 9 of 11	NP_001276020.1
	ZMYM1	NM_001289088.2		c.1009C>G	p.Pro337Ala	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.1009C>G	p.Pro337Ala	missense	Exon 8 of 10	ENSP00000352920.4	Q5SVZ6
	ZMYM1	ENST00000373330.1	TSL:1	c.1009C>G	p.Pro337Ala	missense	Exon 9 of 11	ENSP00000362427.1	Q5SVZ6
	ZMYM1	ENST00000373329.5	TSL:1	n.965C>G		non_coding_transcript_exon	Exon 7 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454678 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722762

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39432

South Asian (SAS) AF: 0.00 AC: 0 AN: 85202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107374

Other (OTH) AF: 0.00 AC: 0 AN: 60054

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0062	T
Eigen	Benign	0.041
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.21
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.040
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.78	T
Polyphen		0.31	B
Vest4		0.27
MutPred		0.41		Loss of stability (P = 0.0045)
MVP		0.18
MPC		0.29
ClinPred		0.66	D
GERP RS		4.6
Varity_R		0.037
gMVP		0.20
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs373549977; hg19: chr1-35577420;