NM_201599.3:c.2315-277T>G

Variant names:

• chrX-71246969-A-C
• rs5937076
• NM_201599.3:c.2315-277T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201599.3(ZMYM3):​c.2315-277T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZMYM3 NM_201599.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543
• Publications: 2 publications found

Genes affected

ZMYM3 (HGNC:13054): (zinc finger MYM-type containing 3) This gene is located on the X chromosome and is subject to X inactivation. It is highly conserved in vertebrates and most abundantly expressed in the brain. The encoded protein is a component of histone deacetylase-containing multiprotein complexes that function through modifying chromatin structure to keep genes silent. A chromosomal translocation (X;13) involving this gene is associated with X-linked cognitive disability. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2010]

ZMYM3 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, X-linked 112

  Inheritance: XL Classification: MODERATE Submitted by: G2P
• intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics
• syndromic intellectual disability

  Inheritance: XL Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM3	NM_201599.3	MANE Select	c.2315-277T>G		intron	N/A	NP_963893.1
	ZMYM3	NM_005096.3		c.2315-277T>G		intron	N/A	NP_005087.1
	ZMYM3	NM_001171162.1		c.2315-277T>G		intron	N/A	NP_001164633.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM3	ENST00000314425.9	TSL:1 MANE Select	c.2315-277T>G		intron	N/A	ENSP00000322845.5
	ZMYM3	ENST00000373998.5	TSL:1	c.2315-277T>G		intron	N/A	ENSP00000363110.1
	ZMYM3	ENST00000373988.5	TSL:5	c.2321-277T>G		intron	N/A	ENSP00000363100.1

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.85
PhyloP100		0.54

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: rs5937076; hg19: chrX-70466819;