rs142613783

Positions:

• chr3-50341826-G-A
• chr3-50341826-G-C

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.1105C>T​(p.Arg369Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00637 in 1,613,930 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (49 hom.)
• Consequence: ZMYND10 NM_015896.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

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=0.00856331).
• BP6: Variant 3-50341826-G-A is Benign according to our data. Variant chr3-50341826-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-50341826-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00508 (774/152370) while in subpopulation NFE AF= 0.00904 (615/68036). AF 95% confidence interval is 0.00845. There are 7 homozygotes in gnomad4. There are 332 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.1105C>T	p.Arg369Trp	missense_variant	10/12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.1090C>T	p.Arg364Trp	missense_variant	9/11		NP_001295308.1
ZMYND10	XM_005265216.4	c.868C>T	p.Arg290Trp	missense_variant	9/11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8	c.1105C>T	p.Arg369Trp	missense_variant	10/12	1	NM_015896.4	ENSP00000231749	P1
ZMYND10-AS1	ENST00000440013.1	n.123+598G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 775 AN: 152252 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00351

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00904

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00541 AC: 1357 AN: 251050 Hom.: 5 AF XY: 0.00555 AC XY: 754 AN XY: 135780

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.0104

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00366

Gnomad FIN exome AF: 0.00389

Gnomad NFE exome AF: 0.00857

Gnomad OTH exome AF: 0.00490

GnomAD4 exome AF: 0.00650 AC: 9499 AN: 1461560 Hom.: 49 Cov.: 32 AF XY: 0.00667 AC XY: 4850 AN XY: 727052

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00968

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00352

Gnomad4 FIN exome AF: 0.00449

Gnomad4 NFE exome AF: 0.00737

Gnomad4 OTH exome AF: 0.00705

GnomAD4 genome AF: 0.00508 AC: 774 AN: 152370 Hom.: 7 Cov.: 33 AF XY: 0.00446 AC XY: 332 AN XY: 74518

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.00348

Gnomad4 NFE AF: 0.00904

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00726 Hom.: 10

Bravo AF: 0.00427

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00779 AC: 67

ExAC AF: 0.00568 AC: 689

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00720

EpiControl AF: 0.00593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 2022

This variant is associated with the following publications: (PMID: 26824761) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.
Eigen	Benign	0.12
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.60
MVP		0.15
MPC		0.41
ClinPred		0.033	T
GERP RS		2.2
Varity_R		0.29
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs142613783; hg19: chr3-50379257; COSMIC: COSV104572892; COSMIC: COSV104572892;