17-4740915-G-C

Position:

• chr17-4740915-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136046.3(ZMYND15):​c.367G>C​(p.Glu123Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYND15 NM_001136046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

Genes affected

ZMYND15 (HGNC:20997): (zinc finger MYND-type containing 15) This gene encodes a MYND-containing zinc-binding protein with a nuclear localization sequence. A similar gene in mice has been shown to act as a testis-specific transcriptional repressor by recruiting histone deacetylase enzymes to regulate spatiotemporal expression of many haploid genes. This protein may play an important role in spermatogenesis. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092868656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYND15	NM_001136046.3	c.367G>C	p.Glu123Gln	missense_variant	2/14	ENST00000433935.6	NP_001129518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND15	ENST00000433935.6	c.367G>C	p.Glu123Gln	missense_variant	2/14	2	NM_001136046.3	ENSP00000391742	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.367G>C (p.E123Q) alteration is located in exon 2 (coding exon 1) of the ZMYND15 gene. This alteration results from a G to C substitution at nucleotide position 367, causing the glutamic acid (E) at amino acid position 123 to be replaced by a glutamine (Q). 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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.044	.;T;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.66	T;T;T;.
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.14	N;N;.;.
REVEL	Benign	0.061
Sift	Benign	0.21	T;T;.;.
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.89	.;P;.;.
Vest4		0.30
MutPred		0.090		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.16
MPC		0.44
ClinPred		0.11	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.11

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: chr17-4644210;