3-50341643-C-T

Position:

chr3-50341643-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015896.4(ZMYND10):c.1178G>A(p.Arg393His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ZMYND10
NM_015896.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.836

Variant links:

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 links:

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

ZMYND10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.212737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZMYND10	NM_015896.4 linkuse as main transcript	c.1178G>A	p.Arg393His	missense_variant	11/12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2 linkuse as main transcript	c.1163G>A	p.Arg388His	missense_variant	10/11		NP_001295308.1
ZMYND10	XM_005265216.4 linkuse as main transcript	c.941G>A	p.Arg314His	missense_variant	10/11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8 linkuse as main transcript	c.1178G>A	p.Arg393His	missense_variant	11/12	1	NM_015896.4	ENSP00000231749	P1	O75800-1
ZMYND10-AS1	ENST00000440013.1 linkuse as main transcript	n.123+415C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251340

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 26, 2021

This sequence change replaces arginine with histidine at codon 393 of the ZMYND10 protein (p.Arg393His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs200276907, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with ZMYND10-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

0.75

D;D

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

D;N

REVEL

Benign

0.054

Sift

Benign

0.090

T;T

Sift4G

Uncertain

0.060

T;D

Polyphen

0.0020

B;B

Vest4

0.28

MVP

0.16

MPC

0.20

ClinPred

0.19

GERP RS

0.019

Varity_R

0.078

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over