9-137583101-A-C

Position:

• chr9-137583101-A-C

Variant summary

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

The NM_138462.3(ZMYND19):​c.422T>G​(p.Phe141Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZMYND19 NM_138462.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.51

Genes affected

ZMYND19 (HGNC:21146): (zinc finger MYND-type containing 19) ZMYND19 is a MYND zinc finger domain-containing protein that binds to the C terminus of melanin-concentrating hormone receptor-1 (MCHR1; MIM 601751) (Bachner et al., 2002 [PubMed 12208518]), and to the N termini of alpha-tubulin (TUBA1; MIM 191110), and beta-tubulin (TUBB; MIM 191130) (Francke et al., 2005 [PubMed 16039987]).[supplied by OMIM, Mar 2008]

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	UniProt
ZMYND19	NM_138462.3	c.422T>G	p.Phe141Cys	missense_variant	5/6	ENST00000298585.3
ZMYND19	XM_005266052.5	c.605T>G	p.Phe202Cys	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND19	ENST00000298585.3	c.422T>G	p.Phe141Cys	missense_variant	5/6	1	NM_138462.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251474 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 0.00000205 AC: 3 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	0.00020	T
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.040	D
Polyphen		0.97	D
Vest4		0.71
MutPred		0.51		Loss of helix (P = 0.0167);
MVP		0.093
MPC		2.0
ClinPred		0.94	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.86

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: rs1278543212; hg19: chr9-140477553;