rs185474627

Variant names:

• chr3-50342393-T-A
• rs185474627
• NM_015896.4:c.873+4A>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015896.4(ZMYND10):​c.873+4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00087 in 1,569,298 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00082 (6 hom.)
• Consequence: ZMYND10 NM_015896.4 splice_region, intron
• Scores: Splicing: ADA: 0.4796
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.702
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-50342393-T-A is Benign according to our data. Variant chr3-50342393-T-A is described in ClinVar as Benign. ClinVar VariationId is 454844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR,AD gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND10	NM_015896.4	MANE Select	c.873+4A>T		splice_region intron	N/A	NP_056980.2
	ZMYND10	NM_001308379.2		c.858+4A>T		splice_region intron	N/A	NP_001295308.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND10	ENST00000231749.8	TSL:1 MANE Select	c.873+4A>T		splice_region intron	N/A	ENSP00000231749.3
	ZMYND10	ENST00000360165.7	TSL:1	c.858+4A>T		splice_region intron	N/A	ENSP00000353289.3
	ZMYND10	ENST00000442887.1	TSL:1	c.744+4A>T		splice_region intron	N/A	ENSP00000393687.1

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 207 AN: 151942 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.00135 AC: 248 AN: 183094 AF XY: 0.00133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000737

Gnomad ASJ exome AF: 0.000112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0116

Gnomad NFE exome AF: 0.000581

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.000817 AC: 1158 AN: 1417240 Hom.: 6 Cov.: 32 AF XY: 0.000804 AC XY: 564 AN XY: 701360

African (AFR) AF: 0.0000310 AC: 1 AN: 32282

American (AMR) AF: 0.0000527 AC: 2 AN: 37948

Ashkenazi Jewish (ASJ) AF: 0.0000786 AC: 2 AN: 25458

East Asian (EAS) AF: 0.00 AC: 0 AN: 36780

South Asian (SAS) AF: 0.0000490 AC: 4 AN: 81708

European-Finnish (FIN) AF: 0.0107 AC: 542 AN: 50422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5482

European-Non Finnish (NFE) AF: 0.000526 AC: 573 AN: 1088502

Other (OTH) AF: 0.000580 AC: 34 AN: 58658

GnomAD4 genome AF: 0.00136 AC: 207 AN: 152058 Hom.: 1 Cov.: 33 AF XY: 0.00182 AC XY: 135 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.0127 AC: 134 AN: 10592

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

European-Non Finnish (NFE) AF: 0.00104 AC: 71 AN: 67944

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.00126 Hom.: 1

Bravo AF: 0.000276

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	ZMYND10-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		-0.70
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.48
dbscSNV1_RF	Benign	0.62
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: rs185474627; hg19: chr3-50379824;