1-35370375-C-T

Variant summary

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

The NM_005095.3(ZMYM4):​c.929C>T​(p.Pro310Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Consequence

ZMYM4
NM_005095.3 missense

Scores

11
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74
Variant links:
Genes affected
ZMYM4 (HGNC:13055): (zinc finger MYM-type containing 4) Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
ZMYM4NM_005095.3 linkc.929C>T p.Pro310Leu missense_variant Exon 7 of 30 ENST00000314607.11 NP_005086.2 Q5VZL5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZMYM4ENST00000314607.11 linkc.929C>T p.Pro310Leu missense_variant Exon 7 of 30 2 NM_005095.3 ENSP00000322915.6 Q5VZL5-1
ZMYM4ENST00000457946.1 linkc.173C>T p.Pro58Leu missense_variant Exon 3 of 24 5 ENSP00000400506.1 H7C1I7
ZMYM4ENST00000482131.1 linkn.162C>T non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
25

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.929C>T (p.P310L) alteration is located in exon 7 (coding exon 7) of the ZMYM4 gene. This alteration results from a C to T substitution at nucleotide position 929, causing the proline (P) at amino acid position 310 to be replaced by a leucine (L). 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
0.35
BayesDel_addAF
Benign
-0.031
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.44
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.13
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.024
D
Polyphen
0.91
P
Vest4
0.60
MutPred
0.21
Gain of helix (P = 0.0325);
MVP
0.043
MPC
0.093
ClinPred
0.90
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-35835976; API