3-50341643-C-A

Variant names:

• chr3-50341643-C-A
• rs200276907
• NM_015896.4:c.1178G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015896.4(ZMYND10):​c.1178G>T​(p.Arg393Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R393C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ZMYND10 NM_015896.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.1178G>T	p.Arg393Leu	missense_variant	Exon 11 of 12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.1163G>T	p.Arg388Leu	missense_variant	Exon 10 of 11		NP_001295308.1
ZMYND10	XM_005265216.4	c.941G>T	p.Arg314Leu	missense_variant	Exon 10 of 11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8	c.1178G>T	p.Arg393Leu	missense_variant	Exon 11 of 12	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		0.84
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.26
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.071	T;T
Polyphen		0.24	B;B
Vest4		0.46
MutPred		0.56		Loss of disorder (P = 0.0244);.;
MVP		0.11
MPC		0.21
ClinPred		0.94	D
GERP RS		0.019
Varity_R		0.31
gMVP		0.63
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200276907; hg19: chr3-50379074;