rs148328402

chr3-50341912-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015896.4(ZMYND10):c.1019G>A(p.Arg340Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,614,188 control chromosomes in the GnomAD database, including 22 homozygotes. 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R340W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (20 hom.)
• Consequence: ZMYND10 NM_015896.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.60

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070642233).
• BP6: Variant 3-50341912-C-T is Benign according to our data. Variant chr3-50341912-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-50341912-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00254 (387/152384) while in subpopulation NFE AF= 0.00369 (251/68038). AF 95% confidence interval is 0.00331. There are 2 homozygotes in gnomad4. There are 175 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND10	NM_015896.4	c.1019G>A	p.Arg340Gln	missense_variant	10/12	ENST00000231749.8
ZMYND10	NM_001308379.2	c.1004G>A	p.Arg335Gln	missense_variant	9/11
ZMYND10	XM_005265216.4	c.782G>A	p.Arg261Gln	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND10	ENST00000231749.8	c.1019G>A	p.Arg340Gln	missense_variant	10/12	1	NM_015896.4	P1
ZMYND10-AS1	ENST00000440013.1	n.123+684C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 387 AN: 152266 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00369

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00281 AC: 706 AN: 251174 Hom.: 3 AF XY: 0.00281 AC XY: 382 AN XY: 135838

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.00855

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.00360

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.00268 AC: 3918 AN: 1461804 Hom.: 20 Cov.: 32 AF XY: 0.00273 AC XY: 1984 AN XY: 727198

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.00903

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00147

Gnomad4 FIN exome AF: 0.00157

Gnomad4 NFE exome AF: 0.00274

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.00254 AC: 387 AN: 152384 Hom.: 2 Cov.: 33 AF XY: 0.00235 AC XY: 175 AN XY: 74526

Gnomad4 AFR AF: 0.000721

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00369

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00335 Hom.: 2

Bravo AF: 0.00296

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00453 AC: 39

ExAC AF: 0.00275 AC: 334

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00528

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 22 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 17, 2021

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ZMYND10: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.0071	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.52	D;D
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.051
Sift	Benign	0.33	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.010	B;B
Vest4		0.30
MVP		0.072
MPC		0.19
ClinPred		0.0087	T
GERP RS		4.1
Varity_R		0.075
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs148328402; hg19: chr3-50379343; COSMIC: COSV51600830; COSMIC: COSV51600830;