chr1-35381712-A-G

Variant names:

• chr1-35381712-A-G
• NM_005095.3:c.1523A>G

Variant summary

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

The NM_005095.3(ZMYM4):​c.1523A>G​(p.Gln508Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZMYM4 NM_005095.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93
• 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]

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.1523A>G	p.Gln508Arg	missense	Exon 9 of 30	NP_005086.2
	ZMYM4	NM_001375653.1		c.1532A>G	p.Gln511Arg	missense	Exon 9 of 30	NP_001362582.1
	ZMYM4	NM_001350138.2		c.1427A>G	p.Gln476Arg	missense	Exon 10 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.1523A>G	p.Gln508Arg	missense	Exon 9 of 30	ENSP00000322915.6	Q5VZL5-1
	ZMYM4	ENST00000933225.1		c.1523A>G	p.Gln508Arg	missense	Exon 9 of 30	ENSP00000603284.1
	ZMYM4	ENST00000933226.1		c.1523A>G	p.Gln508Arg	missense	Exon 9 of 30	ENSP00000603285.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

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	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Benign	0.87
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0072	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.9
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.081
Sift	Benign	0.084	T
Sift4G	Benign	0.20	T
Polyphen		0.41	B
Vest4		0.68
MutPred		0.50		Loss of ubiquitination at K510 (P = 0.0261)
MVP		0.068
MPC		1.4
ClinPred		0.49	T
GERP RS		5.3
Varity_R		0.18
gMVP		0.52
Mutation Taster		=90/10	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

hg19: chr1-35847313;