chr1-35387243-C-A

Position:

• chr1-35387243-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005095.3(ZMYM4):​c.2077C>A​(p.Leu693Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMYM4 NM_005095.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30462208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYM4	NM_005095.3	c.2077C>A	p.Leu693Ile	missense_variant	12/30	ENST00000314607.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYM4	ENST00000314607.11	c.2077C>A	p.Leu693Ile	missense_variant	12/30	2	NM_005095.3	P1
ZMYM4	ENST00000457946.1	c.1057C>A	p.Leu353Ile	missense_variant	6/24	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.2077C>A (p.L693I) alteration is located in exon 12 (coding exon 12) of the ZMYM4 gene. This alteration results from a C to A substitution at nucleotide position 2077, causing the leucine (L) at amino acid position 693 to be replaced by an isoleucine (I). 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	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.79	D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.098
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.89	P
Vest4		0.39
MutPred		0.47		Loss of ubiquitination at K697 (P = 0.0787);
MVP		0.10
MPC		1.3
ClinPred		0.56	D
GERP RS		5.7
Varity_R		0.15
gMVP		0.32

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: chr1-35852844; COSMIC: COSV58909508;