rs1486500328

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-35359411-A-G
• chr1-35359411-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005095.3(ZMYM4):​c.572A>G​(p.Asp191Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000636 in 1,573,076 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000063 (1 hom.)
• Consequence: ZMYM4 NM_005095.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

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>G	p.Asp191Gly	missense	Exon 3 of 30	NP_005086.2
	ZMYM4	NM_001375653.1		c.581A>G	p.Asp194Gly	missense	Exon 3 of 30	NP_001362582.1
	ZMYM4	NM_001350138.2		c.476A>G	p.Asp159Gly	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>G	p.Asp191Gly	missense	Exon 3 of 30	ENSP00000322915.6	Q5VZL5-1
	ZMYM4	ENST00000933225.1		c.572A>G	p.Asp191Gly	missense	Exon 3 of 30	ENSP00000603284.1
	ZMYM4	ENST00000933226.1		c.572A>G	p.Asp191Gly	missense	Exon 3 of 30	ENSP00000603285.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000949 AC: 2 AN: 210706 AF XY: 0.00000867

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000197

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000633 AC: 9 AN: 1420970 Hom.: 1 Cov.: 31 AF XY: 0.00000283 AC XY: 2 AN XY: 705754

African (AFR) AF: 0.0000646 AC: 2 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: 0.00000637 AC: 7 AN: 1099740

Other (OTH) AF: 0.00 AC: 0 AN: 58536

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.31
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		6.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.68
MutPred		0.24		Loss of ubiquitination at K188 (P = 0.0127)
MVP		0.10
MPC		0.19
ClinPred		0.61	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.52
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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;