1-35370375-C-T

Variant names:

• chr1-35370375-C-T
• NM_005095.3:c.929C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74

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 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
ZMYM4	NM_005095.3	c.929C>T	p.Pro310Leu	missense_variant	Exon 7 of 30	ENST00000314607.11	NP_005086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM4	ENST00000314607.11	c.929C>T	p.Pro310Leu	missense_variant	Exon 7 of 30	2	NM_005095.3	ENSP00000322915.6
ZMYM4	ENST00000457946.1	c.173C>T	p.Pro58Leu	missense_variant	Exon 3 of 24	5		ENSP00000400506.1
ZMYM4	ENST00000482131.1	n.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

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;