rs114377074

Variant names:

• chr3-50343622-A-G
• rs114377074
• NM_015896.4:c.319-6T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015896.4(ZMYND10):​c.319-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,614,134 control chromosomes in the GnomAD database, including 80 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 0.013 (47 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (33 hom.)
• Consequence: ZMYND10 NM_015896.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003235
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-50343622-A-G is Benign according to our data. Variant chr3-50343622-A-G is described in ClinVar as Benign. ClinVar VariationId is 241068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0127 (1940/152288) while in subpopulation AFR AF = 0.0443 (1841/41542). AF 95% confidence interval is 0.0426. There are 47 homozygotes in GnomAd4. There are 965 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 47 AD,AR 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND10	NM_015896.4	MANE Select	c.319-6T>C		splice_region intron	N/A	NP_056980.2
	ZMYND10	NM_001308379.2		c.319-6T>C		splice_region intron	N/A	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.319-6T>C		splice_region intron	N/A	ENSP00000231749.3	O75800-1
	ZMYND10	ENST00000360165.7	TSL:1	c.319-6T>C		splice_region intron	N/A	ENSP00000353289.3	O75800-2
	ZMYND10	ENST00000442887.1	TSL:1	c.190-6T>C		splice_region intron	N/A	ENSP00000393687.1	C9JUQ8

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1939 AN: 152170 Hom.: 47 Cov.: 33

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00325 AC: 818 AN: 251354 AF XY: 0.00233

Gnomad AFR exome AF: 0.0460

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00132 AC: 1924 AN: 1461846 Hom.: 33 Cov.: 33 AF XY: 0.00110 AC XY: 803 AN XY: 727224

African (AFR) AF: 0.0486 AC: 1626 AN: 33480

American (AMR) AF: 0.00186 AC: 83 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1112008

Other (OTH) AF: 0.00288 AC: 174 AN: 60394

GnomAD4 genome AF: 0.0127 AC: 1940 AN: 152288 Hom.: 47 Cov.: 33 AF XY: 0.0130 AC XY: 965 AN XY: 74466

African (AFR) AF: 0.0443 AC: 1841 AN: 41542

American (AMR) AF: 0.00516 AC: 79 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00656 Hom.: 10

Bravo AF: 0.0155

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.56
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.018
Splicevardb		2.0
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: rs114377074; hg19: chr3-50381053;