X-71246969-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_201599.3(ZMYM3):​c.2315-277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 110,060 control chromosomes in the GnomAD database, including 6,995 homozygotes. There are 12,309 hemizygotes in GnomAD. 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: 𝑓 0.39 (6995 hom., 12309 hem., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

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>C		intron	N/A	NP_963893.1
	ZMYM3	NM_005096.3		c.2315-277T>C		intron	N/A	NP_005087.1
	ZMYM3	NM_001171162.1		c.2315-277T>C		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>C		intron	N/A	ENSP00000322845.5
	ZMYM3	ENST00000373998.5	TSL:1	c.2315-277T>C		intron	N/A	ENSP00000363110.1
	ZMYM3	ENST00000373988.5	TSL:5	c.2321-277T>C		intron	N/A	ENSP00000363100.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 42338 AN: 110004 Hom.: 6987 Cov.: 22

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.385 AC: 42376 AN: 110060 Hom.: 6995 Cov.: 22 AF XY: 0.380 AC XY: 12309 AN XY: 32360

African (AFR) AF: 0.576 AC: 17380 AN: 30148

American (AMR) AF: 0.536 AC: 5513 AN: 10295

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 628 AN: 2640

East Asian (EAS) AF: 0.702 AC: 2424 AN: 3454

South Asian (SAS) AF: 0.502 AC: 1297 AN: 2583

European-Finnish (FIN) AF: 0.226 AC: 1321 AN: 5837

Middle Eastern (MID) AF: 0.304 AC: 66 AN: 217

European-Non Finnish (NFE) AF: 0.247 AC: 13014 AN: 52727

Other (OTH) AF: 0.401 AC: 596 AN: 1488

Alfa AF: 0.327 Hom.: 21614

Bravo AF: 0.427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.80
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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;