Genetic Variant NM_015896.4:c.1248-30T>C (chr3-50341515-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015896.4(ZMYND10):c.1248-30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,614,102 control chromosomes in the GnomAD database, including 28,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4251 hom., cov: 33)

Exomes 𝑓: 0.15 ( 24186 hom. )

Consequence

ZMYND10
NM_015896.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.28

Publications

25 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-50341515-A-G is Benign according to our data. Variant chr3-50341515-A-G is described in ClinVar as Benign. ClinVar VariationId is 1231903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

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.1248-30T>C		intron	N/A	NP_056980.2
	ZMYND10	NM_001308379.2		c.1233-30T>C		intron	N/A	NP_001295308.1	O75800-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZMYND10	ENST00000231749.8	TSL:1 MANE Select	c.1248-30T>C	intron	N/A	ENSP00000231749.3	O75800-1
ZMYND10	ENST00000360165.7	TSL:1	c.1233-30T>C	intron	N/A	ENSP00000353289.3	O75800-2
ZMYND10	ENST00000874785.1		c.1287-30T>C	intron	N/A	ENSP00000544844.1

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30644

AN:

152122

Hom.:

4241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.665

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.188

GnomAD2 exomes

AF:

0.223

AC:

56025

AN:

251414

AF XY:

0.202

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.489

Gnomad ASJ exome

AF:

0.0783

Gnomad EAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.147

AC:

214665

AN:

1461862

Hom.:

24186

Cov.:

AF XY:

0.144

AC XY:

104539

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.271

AC:

9088

AN:

33480

American (AMR)

AF:

0.468

AC:

20948

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0801

AC:

2093

AN:

26136

East Asian (EAS)

AF:

0.612

AC:

24305

AN:

39700

South Asian (SAS)

AF:

0.119

AC:

10272

AN:

86250

European-Finnish (FIN)

AF:

0.182

AC:

9712

AN:

53414

Middle Eastern (MID)

AF:

0.117

AC:

674

AN:

5768

European-Non Finnish (NFE)

AF:

0.115

AC:

127426

AN:

1112004

Other (OTH)

AF:

0.168

AC:

10147

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

11902

23804

35707

47609

59511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5124

10248

15372

20496

25620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.202

AC:

30708

AN:

152240

Hom.:

4251

Cov.:

AF XY:

0.208

AC XY:

15472

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.262

AC:

10886

AN:

41550

American (AMR)

AF:

0.349

AC:

5333

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0778

AC:

270

AN:

3470

East Asian (EAS)

AF:

0.665

AC:

3440

AN:

5176

South Asian (SAS)

AF:

0.124

AC:

599

AN:

4828

European-Finnish (FIN)

AF:

0.179

AC:

1903

AN:

10608

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7664

AN:

67994

Other (OTH)

AF:

0.192

AC:

406

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1231

2461

3692

4922

6153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.157

Hom.:

615

Bravo

AF:

0.223

Asia WGS

AF:

0.317

AC:

1101

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.56

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over