X-71240941-C-A

Variant names:

• chrX-71240941-C-A
• NM_201599.3:c.4088G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_201599.3(ZMYM3):​c.4088G>T​(p.Arg1363Leu) variant causes a missense 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27423722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM3	NM_201599.3	c.4088G>T	p.Arg1363Leu	missense_variant	Exon 25 of 25	ENST00000314425.9	NP_963893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM3	ENST00000314425.9	c.4088G>T	p.Arg1363Leu	missense_variant	Exon 25 of 25	1	NM_201599.3	ENSP00000322845.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T;.;T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.2	L;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.037	D;D;T;D
Sift4G	Benign	0.076	T;T;T;T
Polyphen		0.94	P;D;.;.
Vest4		0.23
MutPred		0.29		Loss of disorder (P = 0.0414);.;.;.;
MVP		0.18
ClinPred		0.83	D
GERP RS		4.3
Varity_R		0.37
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70460791;