NM_024772.5:c.305C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024772.5(ZMYM1):​c.305C>G​(p.Ala102Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

ZMYM1
NM_024772.5 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34
Variant links:
Genes affected
ZMYM1 (HGNC:26253): (zinc finger MYM-type containing 1) Predicted to enable protein dimerization activity and zinc ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZMYM1NM_024772.5 linkc.305C>G p.Ala102Gly missense_variant Exon 4 of 10 ENST00000359858.9 NP_079048.3 Q5SVZ6Q9H5R2B4DSJ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZMYM1ENST00000359858.9 linkc.305C>G p.Ala102Gly missense_variant Exon 4 of 10 1 NM_024772.5 ENSP00000352920.4 Q5SVZ6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
38
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.305C>G (p.A102G) alteration is located in exon 4 (coding exon 3) of the ZMYM1 gene. This alteration results from a C to G substitution at nucleotide position 305, causing the alanine (A) at amino acid position 102 to be replaced by a glycine (G). 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
Uncertain
0.41
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;.;T;T;T
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;D;.;.
M_CAP
Benign
0.043
D
MetaRNN
Pathogenic
0.87
D;D;D;D;D
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.6
M;.;M;M;M
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-3.4
.;D;.;N;N
REVEL
Uncertain
0.36
Sift
Uncertain
0.0020
.;D;.;D;D
Sift4G
Uncertain
0.037
.;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.66, 0.66, 0.66
MutPred
0.84
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.56
MPC
0.67
ClinPred
0.98
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.55
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-35563053; API