Genetic Variant NM_138462.3:c.287A>G (chr9-137587039-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_138462.3(ZMYND19):c.287A>G(p.Asn96Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZMYND19
NM_138462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Variant links:

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]

ZMYND19 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND19	NM_138462.3 link	c.287A>G	p.Asn96Ser	missense_variant	Exon 4 of 6	ENST00000298585.3	NP_612471.1	Q96E35
ZMYND19	XM_005266052.5 link	c.470A>G	p.Asn157Ser	missense_variant	Exon 4 of 6		XP_005266109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND19	ENST00000298585.3 link	c.287A>G	p.Asn96Ser	missense_variant	Exon 4 of 6	1	NM_138462.3	ENSP00000298585.2		Q96E35
ZMYND19	ENST00000471957.1 link	n.1233A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.287A>G (p.N96S) alteration is located in exon 4 (coding exon 4) of the ZMYND19 gene. This alteration results from a A to G substitution at nucleotide position 287, causing the asparagine (N) at amino acid position 96 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.78

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.6

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.3

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.82

MutPred

0.32

Loss of sheet (P = 0.0315);

MVP

0.46

MPC

1.3

ClinPred

0.99

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over