X-71241303-T-C

Variant names:

• chrX-71241303-T-C
• NM_201599.3:c.3844A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_201599.3(ZMYM3):​c.3844A>G​(p.Ile1282Val) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ZMYM3 NM_201599.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.303

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023006469).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM3	NM_201599.3	c.3844A>G	p.Ile1282Val	missense_variant	Exon 24 of 25	ENST00000314425.9	NP_963893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM3	ENST00000314425.9	c.3844A>G	p.Ile1282Val	missense_variant	Exon 24 of 25	1	NM_201599.3	ENSP00000322845.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3844A>G (p.I1282V) alteration is located in exon 24 (coding exon 23) of the ZMYM3 gene. This alteration results from a A to G substitution at nucleotide position 3844, causing the isoleucine (I) at amino acid position 1282 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.41
DEOGEN2	Benign	0.056	T;.;T;T
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.75	T;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.023	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.20	N;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.60	N;N;N;N
REVEL	Benign	0.028
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.096
MutPred		0.20		Gain of MoRF binding (P = 0.2978);.;.;.;
MVP		0.14
ClinPred		0.037	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.64

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-70461153;