rs1192082694

Variant names:

• chr13-19835661-A-T
• rs1192082694
• NM_001142684.2:c.1067T>A

Variant summary

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

The NM_001142684.2(ZMYM5):​c.1067T>A​(p.Val356Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMYM5 NM_001142684.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.92
• Publications: 0 publications found

Genes affected

ZMYM5 (HGNC:13029): (zinc finger MYM-type containing 5) Predicted to enable zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM5 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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_001142684.2. 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
	ZMYM5	NM_001142684.2	MANE Select	c.1067T>A	p.Val356Glu	missense	Exon 7 of 8	NP_001136156.1	Q9UJ78-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM5	ENST00000337963.9	TSL:5 MANE Select	c.1067T>A	p.Val356Glu	missense	Exon 7 of 8	ENSP00000337034.4	Q9UJ78-4
	ZMYM5	ENST00000382909.5	TSL:1	n.923T>A		non_coding_transcript_exon	Exon 4 of 5
	ZMYM5	ENST00000854552.1		c.1067T>A	p.Val356Glu	missense	Exon 6 of 7	ENSP00000524611.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		8.9
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.32
Sift	Benign	0.037	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.58
MutPred		0.63		Gain of disorder (P = 0.0063)
MVP		0.085
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.59
Mutation Taster		=72/28	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: rs1192082694; hg19: chr13-20409801;