NM_201599.3:c.3552G>A

Variant names:

• chrX-71242420-C-T
• rs375862549
• NM_201599.3:c.3552G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_201599.3(ZMYM3):​c.3552G>A​(p.Thr1184Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,208,823 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000020 (0 hom. 7 hem.)
• Consequence: ZMYM3 NM_201599.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.96
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.96 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 7 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM3	NM_201599.3	MANE Select	c.3552G>A	p.Thr1184Thr	synonymous	Exon 23 of 25	NP_963893.1	Q14202-1
	ZMYM3	NM_005096.3		c.3552G>A	p.Thr1184Thr	synonymous	Exon 23 of 25	NP_005087.1	Q14202-1
	ZMYM3	NM_001171162.1		c.3516G>A	p.Thr1172Thr	synonymous	Exon 23 of 25	NP_001164633.1	Q14202-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM3	ENST00000314425.9	TSL:1 MANE Select	c.3552G>A	p.Thr1184Thr	synonymous	Exon 23 of 25	ENSP00000322845.5	Q14202-1
	ZMYM3	ENST00000373998.5	TSL:1	c.3516G>A	p.Thr1172Thr	synonymous	Exon 23 of 25	ENSP00000363110.1	Q14202-2
	ZMYM3	ENST00000373988.5	TSL:5	c.3558G>A	p.Thr1186Thr	synonymous	Exon 23 of 25	ENSP00000363100.1	A6NHB5

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111796 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000112 AC: 2 AN: 178934 AF XY: 0.0000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000253

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000201 AC: 22 AN: 1097027 Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 7 AN XY: 362435

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.00 AC: 0 AN: 35152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19348

East Asian (EAS) AF: 0.00 AC: 0 AN: 30184

South Asian (SAS) AF: 0.00 AC: 0 AN: 53845

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40425

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.0000261 AC: 22 AN: 841490

Other (OTH) AF: 0.00 AC: 0 AN: 46057

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111796 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33952

African (AFR) AF: 0.0000651 AC: 2 AN: 30745

American (AMR) AF: 0.00 AC: 0 AN: 10566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3539

South Asian (SAS) AF: 0.00 AC: 0 AN: 2687

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6071

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53106

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.29
DANN	Benign	0.41
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs375862549; hg19: chrX-70462270;