1-35359411-A-T

Variant names:

• chr1-35359411-A-T
• rs1486500328
• NM_005095.3:c.572A>T

Variant summary

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

The NM_005095.3(ZMYM4):​c.572A>T​(p.Asp191Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,420,970 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. D191G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ZMYM4 NM_005095.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14
• Publications: 0 publications found

Genes affected

ZMYM4 (HGNC:13055): (zinc finger MYM-type containing 4) Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM4-AS1 (HGNC:40624): (ZMYM4 antisense RNA 1)

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_005095.3. 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
	ZMYM4	NM_005095.3	MANE Select	c.572A>T	p.Asp191Val	missense	Exon 3 of 30	NP_005086.2
	ZMYM4	NM_001375653.1		c.581A>T	p.Asp194Val	missense	Exon 3 of 30	NP_001362582.1
	ZMYM4	NM_001350138.2		c.476A>T	p.Asp159Val	missense	Exon 4 of 31	NP_001337067.1	Q5VZL5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM4	ENST00000314607.11	TSL:2 MANE Select	c.572A>T	p.Asp191Val	missense	Exon 3 of 30	ENSP00000322915.6	Q5VZL5-1
	ZMYM4	ENST00000933225.1		c.572A>T	p.Asp191Val	missense	Exon 3 of 30	ENSP00000603284.1
	ZMYM4	ENST00000933226.1		c.572A>T	p.Asp191Val	missense	Exon 3 of 30	ENSP00000603285.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420970 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705754

African (AFR) AF: 0.00 AC: 0 AN: 30936

American (AMR) AF: 0.00 AC: 0 AN: 32338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23608

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 78766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099740

Other (OTH) AF: 0.0000171 AC: 1 AN: 58536

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L
PhyloP100		6.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.33		Loss of ubiquitination at K188 (P = 0.0116)
MVP		0.093
MPC		0.35
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.40
gMVP		0.61
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1486500328; hg19: chr1-35825012;