3-50341601-C-G

Variant names:

• chr3-50341601-C-G
• rs182064110
• NM_015896.4:c.1220G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_015896.4(ZMYND10):​c.1220G>C​(p.Arg407Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,614,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: ZMYND10 NM_015896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 3 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.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015896.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND10	NM_015896.4	MANE Select	c.1220G>C	p.Arg407Pro	missense	Exon 11 of 12	NP_056980.2
	ZMYND10	NM_001308379.2		c.1205G>C	p.Arg402Pro	missense	Exon 10 of 11	NP_001295308.1	O75800-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND10	ENST00000231749.8	TSL:1 MANE Select	c.1220G>C	p.Arg407Pro	missense	Exon 11 of 12	ENSP00000231749.3	O75800-1
	ZMYND10	ENST00000360165.7	TSL:1	c.1205G>C	p.Arg402Pro	missense	Exon 10 of 11	ENSP00000353289.3	O75800-2
	ZMYND10	ENST00000874785.1		c.1259G>C	p.Arg420Pro	missense	Exon 11 of 12	ENSP00000544844.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152274 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251422 AF XY: 0.0000662

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.0000371 AC XY: 27 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152392 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74524

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Pathogenic	4.5	H
PhyloP100		5.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.74
MVP		0.17
MPC		0.81
ClinPred		0.92	D
GERP RS		3.8
Varity_R		0.97
gMVP		0.84
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs182064110; hg19: chr3-50379032;