chr3-50341515-A-G

Variant names:

• chr3-50341515-A-G
• rs1989839
• NM_015896.4:c.1248-30T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.28
• Publications: 25 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: 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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.1248-30T>C		intron_variant	Intron 11 of 11	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.1233-30T>C		intron_variant	Intron 10 of 10		NP_001295308.1
ZMYND10	XM_005265216.4	c.1011-30T>C		intron_variant	Intron 10 of 10		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8	c.1248-30T>C		intron_variant	Intron 11 of 11	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30644 AN: 152122 Hom.: 4241 Cov.: 33

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

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.: 33 AF XY: 0.144 AC XY: 104539 AN XY: 727236

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

GnomAD4 genome AF: 0.202 AC: 30708 AN: 152240 Hom.: 4251 Cov.: 33 AF XY: 0.208 AC XY: 15472 AN XY: 74436

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: 35 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7664 AN: 67994

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.157 Hom.: 615

Bravo AF: 0.223

Asia WGS AF: 0.317 AC: 1101 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.56
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1989839; hg19: chr3-50378946; COSMIC: COSV51602574; COSMIC: COSV51602574;