3-50341197-A-G

Variant names:

• chr3-50341197-A-G
• rs3213621
• NM_015896.4:c.*213T>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.*213T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 653,344 control chromosomes in the GnomAD database, including 8,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2767 hom., cov: 33)
  • Exomes 𝑓: 0.061 (6204 hom.)
• Consequence: ZMYND10 NM_015896.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65
• Publications: 10 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)

RASSF1 (HGNC:9882): (Ras association domain family member 1) This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, May 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-50341197-A-G is Benign according to our data. Variant chr3-50341197-A-G is described in ClinVar as [Benign]. Clinvar id is 1221244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.*213T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.*213T>C		3_prime_UTR_variant	Exon 11 of 11		NP_001295308.1
ZMYND10	XM_005265216.4	c.*213T>C		3_prime_UTR_variant	Exon 11 of 11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8	c.*213T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18061 AN: 152118 Hom.: 2761 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.0994

GnomAD4 exome AF: 0.0615 AC: 30816 AN: 501108 Hom.: 6204 Cov.: 6 AF XY: 0.0566 AC XY: 14846 AN XY: 262152

African (AFR) AF: 0.238 AC: 3194 AN: 13410

American (AMR) AF: 0.329 AC: 6261 AN: 19048

Ashkenazi Jewish (ASJ) AF: 0.00406 AC: 57 AN: 14050

East Asian (EAS) AF: 0.524 AC: 16404 AN: 31296

South Asian (SAS) AF: 0.0115 AC: 538 AN: 46946

European-Finnish (FIN) AF: 0.0451 AC: 1332 AN: 29532

Middle Eastern (MID) AF: 0.00621 AC: 13 AN: 2094

European-Non Finnish (NFE) AF: 0.00322 AC: 1022 AN: 317022

Other (OTH) AF: 0.0720 AC: 1995 AN: 27710

GnomAD4 genome AF: 0.119 AC: 18123 AN: 152236 Hom.: 2767 Cov.: 33 AF XY: 0.125 AC XY: 9289 AN XY: 74444

African (AFR) AF: 0.235 AC: 9774 AN: 41534

American (AMR) AF: 0.272 AC: 4163 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3468

East Asian (EAS) AF: 0.600 AC: 3101 AN: 5172

South Asian (SAS) AF: 0.0216 AC: 104 AN: 4824

European-Finnish (FIN) AF: 0.0469 AC: 497 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00375 AC: 255 AN: 68012

Other (OTH) AF: 0.0998 AC: 211 AN: 2114

Alfa AF: 0.0504 Hom.: 1164

Bravo AF: 0.147

Asia WGS AF: 0.215 AC: 745 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	-0.82
CADD	Benign	0.55
DANN	Benign	0.39
PhyloP100		-1.6
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3213621; hg19: chr3-50378628;