rs373018717

Positions:

• chr3-50341813-C-G
• chr3-50341813-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015896.4(ZMYND10):​c.1118G>C​(p.Arg373Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZMYND10 NM_015896.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYND10	NM_015896.4	c.1118G>C	p.Arg373Pro	missense_variant	10/12	ENST00000231749.8	NP_056980.2
ZMYND10	NM_001308379.2	c.1103G>C	p.Arg368Pro	missense_variant	9/11		NP_001295308.1
ZMYND10	XM_005265216.4	c.881G>C	p.Arg294Pro	missense_variant	9/11		XP_005265273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND10	ENST00000231749.8	c.1118G>C	p.Arg373Pro	missense_variant	10/12	1	NM_015896.4	ENSP00000231749.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250956 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135722

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461524 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727026

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	9.2
DANN	Benign	0.69
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.28	B;B
Vest4		0.74
MutPred		0.55		Loss of MoRF binding (P = 5e-04);.;
MVP		0.10
MPC		0.29
ClinPred		0.12	T
GERP RS		-2.7
Varity_R		0.55
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs373018717; hg19: chr3-50379244; COSMIC: COSV51603976; COSMIC: COSV51603976;