3-50341643-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015896.4(ZMYND10):​c.1178G>C​(p.Arg393Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.1178G>C	p.Arg393Pro	missense_variant	Exon 11 of 12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.1163G>C	p.Arg388Pro	missense_variant	Exon 10 of 11		NP_001295308.1
ZMYND10	XM_005265216.4	c.941G>C	p.Arg314Pro	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>C	p.Arg393Pro	missense_variant	Exon 11 of 12	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		0.84
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.39	B;P
Vest4		0.66
MutPred		0.52		Gain of catalytic residue at P392 (P = 0.0155);.;
MVP		0.19
MPC		0.38
ClinPred		0.96	D
GERP RS		0.019
Varity_R		0.41
gMVP		0.84
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs200276907; hg19: chr3-50379074;