3-50341482-C-A

Variant names:

• chr3-50341482-C-A
• NM_015896.4:c.1251G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015896.4(ZMYND10):​c.1251G>T​(p.Glu417Asp) 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: ZMYND10 NM_015896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.337
• Publications: 0 publications found

Genes affected

ZMYND10 (HGNC:19412): (zinc finger MYND-type containing 10) This gene encodes a protein containing a MYND-type zinc finger domain that likely functions in assembly of the dynein motor. Mutations in this gene can cause primary ciliary dyskinesia. This gene is also considered a tumor suppressor gene and is often mutated, deleted, or hypermethylated and silenced in cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

ZMYND10-AS1 (HGNC:40890): (ZMYND10 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4152706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.1251G>T	p.Glu417Asp	missense_variant	Exon 12 of 12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.1236G>T	p.Glu412Asp	missense_variant	Exon 11 of 11		NP_001295308.1
ZMYND10	XM_005265216.4	c.1014G>T	p.Glu338Asp	missense_variant	Exon 11 of 11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8	c.1251G>T	p.Glu417Asp	missense_variant	Exon 12 of 12	1	NM_015896.4	ENSP00000231749.3

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

Inborn genetic diseases Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1251G>T (p.E417D) alteration is located in exon 12 (coding exon 12) of the ZMYND10 gene. This alteration results from a G to T substitution at nucleotide position 1251, causing the glutamic acid (E) at amino acid position 417 to be replaced by an aspartic acid (D). 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	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		0.34
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.087
Sift	Benign	0.057	T;D
Sift4G	Benign	0.061	T;T
Polyphen		0.013	B;B
Vest4		0.13
MutPred		0.87		Loss of disorder (P = 0.1131);.;
MVP		0.13
MPC		0.20
ClinPred		0.58	D
GERP RS		1.6
Varity_R		0.14
gMVP		0.40
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

hg19: chr3-50378913;