X-71246969-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM3	NM_201599.3	c.2315-277T>C		intron_variant	Intron 13 of 24	ENST00000314425.9	NP_963893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM3	ENST00000314425.9	c.2315-277T>C		intron_variant	Intron 13 of 24	1	NM_201599.3	ENSP00000322845.5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 42338 AN: 110004 Hom.: 6987 Cov.: 22 AF XY: 0.380 AC XY: 12277 AN XY: 32294

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

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.401

Alfa AF: 0.294 Hom.: 12309

Bravo AF: 0.427

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs5937076; hg19: chrX-70466819;