17-4741994-T-C

Position:

• chr17-4741994-T-C

Variant summary

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

The NM_001136046.3(ZMYND15):​c.907T>C​(p.Phe303Leu) 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: 32)
• Consequence: ZMYND15 NM_001136046.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

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.907T>C	p.Phe303Leu	missense_variant	4/14	ENST00000433935.6	NP_001129518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND15	ENST00000433935.6	c.907T>C	p.Phe303Leu	missense_variant	4/14	2	NM_001136046.3	ENSP00000391742.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 14, 2023

The c.907T>C (p.F303L) alteration is located in exon 4 (coding exon 3) of the ZMYND15 gene. This alteration results from a T to C substitution at nucleotide position 907, causing the phenylalanine (F) at amino acid position 303 to be replaced by a leucine (L). 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	0.97
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	.;T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.79	T;T;T;.
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.81	L;L;L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.25	N;N;.;.
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.97	.;D;.;.
Vest4		0.78
MutPred		0.25		Gain of catalytic residue at F303 (P = 0.0395);Gain of catalytic residue at F303 (P = 0.0395);Gain of catalytic residue at F303 (P = 0.0395);Gain of catalytic residue at F303 (P = 0.0395);
MVP		0.72
MPC		0.95
ClinPred		0.89	D
GERP RS		5.2
Varity_R		0.28
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-4645289;