1-35361761-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_005095.3(ZMYM4):​c.812A>G​(p.Lys271Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000311 in 1,607,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ZMYM4
NM_005095.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78
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]
ZMYM4-AS1 (HGNC:40624): (ZMYM4 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1
In a cross_link Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) (size 0) in uniprot entity ZMYM4_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.040412247).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZMYM4NM_005095.3 linkc.812A>G p.Lys271Arg missense_variant Exon 5 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.812A>G p.Lys271Arg missense_variant Exon 5 of 30 2 NM_005095.3 ENSP00000322915.6 Q5VZL5-1
ZMYM4ENST00000457946.1 linkc.56A>G p.Lys19Arg missense_variant Exon 1 of 24 5 ENSP00000400506.1 H7C1I7
ZMYM4ENST00000482131.1 linkn.45A>G non_coding_transcript_exon_variant Exon 1 of 3 2
ZMYM4-AS1ENST00000432683.1 linkn.113-2593T>C intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000821
AC:
2
AN:
243616
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000558
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000897
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000302
AC:
44
AN:
1455630
Hom.:
0
Cov.:
31
AF XY:
0.0000304
AC XY:
22
AN XY:
724148
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000235
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000773
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.812A>G (p.K271R) alteration is located in exon 5 (coding exon 5) of the ZMYM4 gene. This alteration results from a A to G substitution at nucleotide position 812, causing the lysine (K) at amino acid position 271 to be replaced by an arginine (R). 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
0.084
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.036
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.83
N
REVEL
Benign
0.043
Sift
Benign
0.28
T
Sift4G
Benign
0.58
T
Polyphen
0.0
B
Vest4
0.12
MVP
0.043
MPC
0.071
ClinPred
0.26
T
GERP RS
3.4
Varity_R
0.054
gMVP
0.25

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.

Other links and lift over

dbSNP: rs370528397; hg19: chr1-35827362; API