17-4740754-T-C

Position:

• chr17-4740754-T-C

Variant summary

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

The NM_001136046.3(ZMYND15):​c.206T>C​(p.Ile69Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 2.39

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYND15	NM_001136046.3	c.206T>C	p.Ile69Thr	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.206T>C	p.Ile69Thr	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

Apr 12, 2024

The c.206T>C (p.I69T) alteration is located in exon 2 (coding exon 1) of the ZMYND15 gene. This alteration results from a T to C substitution at nucleotide position 206, causing the isoleucine (I) at amino acid position 69 to be replaced by a threonine (T). 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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	.;T;.;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.83	T;T;T;.
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.0	L;L;L;L
MutationTaster	Benign	0.89	D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.58	N;N;.;.
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;D;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		0.65	.;P;.;.
Vest4		0.93
MutPred		0.44		Loss of stability (P = 0.002);Loss of stability (P = 0.002);Loss of stability (P = 0.002);Loss of stability (P = 0.002);
MVP		0.37
MPC		0.65
ClinPred		0.71	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.49

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: chr17-4644049;