Variant 1-34987613-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007167.4(ZMYM6):c.3469C>T(p.Arg1157Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,606,288 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

ZMYM6
NM_007167.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.406

Variant links:

Genes affected

ZMYM6 (HGNC:13050): (zinc finger MYM-type containing 6) Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17983463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM6	NM_007167.4 linkuse as main transcript	c.3469C>T	p.Arg1157Cys	missense_variant	16/16	ENST00000357182.9	NP_009098.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYM6	ENST00000357182.9 linkuse as main transcript	c.3469C>T	p.Arg1157Cys	missense_variant	16/16	1	NM_007167.4	ENSP00000349708	P1	O95789-3
ZMYM6	ENST00000493328.5 linkuse as main transcript	n.4793C>T		non_coding_transcript_exon_variant	15/15	1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000856

AC:

AN:

233780

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

126998

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000686

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1454162

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

722702

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000470

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000199

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 07, 2024

The c.3469C>T (p.R1157C) alteration is located in exon 16 (coding exon 15) of the ZMYM6 gene. This alteration results from a C to T substitution at nucleotide position 3469, causing the arginine (R) at amino acid position 1157 to be replaced by a cysteine (C). 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

Benign

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.78

M_CAP

Benign

0.027

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.22

Sift

Uncertain

0.018

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.19

MutPred

0.52

Gain of methylation at K1156 (P = 0.0209);

MVP

0.15

MPC

0.29

ClinPred

0.91

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.64

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