rs1157869948

Variant names:

• chr13-19835486-T-A
• rs1157869948
• NM_001142684.2:c.1242A>T

Variant summary

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

The NM_001142684.2(ZMYM5):​c.1242A>T​(p.Glu414Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E414K) has been classified 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: 0.185
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20650238).

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.1242A>T	p.Glu414Asp	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.1242A>T	p.Glu414Asp	missense	Exon 7 of 8	ENSP00000337034.4	Q9UJ78-4
	ZMYM5	ENST00000382909.5	TSL:1	n.1098A>T		non_coding_transcript_exon	Exon 4 of 5
	ZMYM5	ENST00000854552.1		c.1242A>T	p.Glu414Asp	missense	Exon 6 of 7	ENSP00000524611.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.053
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.18
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.40	T
Polyphen		0.98	D
Vest4		0.23
MutPred		0.43		Loss of disorder (P = 0.0893)
MVP		0.16
ClinPred		0.81	D
GERP RS		0.99
Varity_R		0.089
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1157869948; hg19: chr13-20409626;