X-71241084-G-A

Variant names:

• chrX-71241084-G-A
• rs2272778
• NM_201599.3:c.3945C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_201599.3(ZMYM3):​c.3945C>T​(p.Asn1315Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,207,394 control chromosomes in the GnomAD database, including 14 homozygotes. There are 1,736 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., 109 hem., cov: 21)
  • Exomes 𝑓: 0.0047 (13 hom. 1627 hem.)
• Consequence: ZMYM3 NM_201599.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-71241084-G-A is Benign according to our data. Variant chrX-71241084-G-A is described in ClinVar as Benign. ClinVar VariationId is 782794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 109 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.3945C>T	p.Asn1315Asn	synonymous	Exon 25 of 25	NP_963893.1	Q14202-1
	ZMYM3	NM_005096.3		c.3945C>T	p.Asn1315Asn	synonymous	Exon 25 of 25	NP_005087.1	Q14202-1
	ZMYM3	NM_001171162.1		c.3909C>T	p.Asn1303Asn	synonymous	Exon 25 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.3945C>T	p.Asn1315Asn	synonymous	Exon 25 of 25	ENSP00000322845.5	Q14202-1
	ZMYM3	ENST00000373998.5	TSL:1	c.3909C>T	p.Asn1303Asn	synonymous	Exon 25 of 25	ENSP00000363110.1	Q14202-2
	ZMYM3	ENST00000373988.5	TSL:5	c.3951C>T	p.Asn1317Asn	synonymous	Exon 25 of 25	ENSP00000363100.1	A6NHB5

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 380 AN: 110692 Hom.: 1 Cov.: 21

Gnomad AFR AF: 0.000427

Gnomad AMI AF: 0.00735

Gnomad AMR AF: 0.000870

Gnomad ASJ AF: 0.00800

Gnomad EAS AF: 0.00256

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00880

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.00201

GnomAD2 exomes AF: 0.00415 AC: 744 AN: 179331 AF XY: 0.00400

Gnomad AFR exome AF: 0.000466

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.00961

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.00509

Gnomad OTH exome AF: 0.00426

GnomAD4 exome AF: 0.00468 AC: 5137 AN: 1096648 Hom.: 13 Cov.: 31 AF XY: 0.00449 AC XY: 1627 AN XY: 362036

African (AFR) AF: 0.000341 AC: 9 AN: 26383

American (AMR) AF: 0.00217 AC: 76 AN: 35080

Ashkenazi Jewish (ASJ) AF: 0.00817 AC: 158 AN: 19340

East Asian (EAS) AF: 0.00683 AC: 206 AN: 30172

South Asian (SAS) AF: 0.00 AC: 0 AN: 53855

European-Finnish (FIN) AF: 0.0113 AC: 455 AN: 40427

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4135

European-Non Finnish (NFE) AF: 0.00483 AC: 4061 AN: 841207

Other (OTH) AF: 0.00371 AC: 171 AN: 46049

GnomAD4 genome AF: 0.00343 AC: 380 AN: 110746 Hom.: 1 Cov.: 21 AF XY: 0.00331 AC XY: 109 AN XY: 32972

African (AFR) AF: 0.000427 AC: 13 AN: 30480

American (AMR) AF: 0.000869 AC: 9 AN: 10362

Ashkenazi Jewish (ASJ) AF: 0.00800 AC: 21 AN: 2624

East Asian (EAS) AF: 0.00257 AC: 9 AN: 3508

South Asian (SAS) AF: 0.00 AC: 0 AN: 2597

European-Finnish (FIN) AF: 0.00880 AC: 52 AN: 5906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.00507 AC: 268 AN: 52865

Other (OTH) AF: 0.00198 AC: 3 AN: 1512

Alfa AF: 0.00470 Hom.: 61

Bravo AF: 0.00275

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.72
PhyloP100		-1.1
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: rs2272778; hg19: chrX-70460934;