chr1-35359268-T-A

Position:

• chr1-35359268-T-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_005095.3(ZMYM4):​c.429T>A​(p.Asp143Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ZMYM4 NM_005095.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538

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)

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZMYM4
• BP4: Computational evidence support a benign effect (MetaRNN=0.05012682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYM4	NM_005095.3	c.429T>A	p.Asp143Glu	missense_variant	3/30	ENST00000314607.11
ZMYM4-AS1	NR_046659.1	n.113-100A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYM4	ENST00000314607.11	c.429T>A	p.Asp143Glu	missense_variant	3/30	2	NM_005095.3	P1
ZMYM4-AS1	ENST00000432683.1	n.113-100A>T		intron_variant, non_coding_transcript_variant		2
ZMYM4	ENST00000441447.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152078 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74292

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.96	N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.084
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.14		Loss of sheet (P = 0.0126);
MVP		0.043
MPC		0.080
ClinPred		0.76	D
GERP RS		4.3
Varity_R		0.050
gMVP		0.056

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1380552187; hg19: chr1-35824869;