1-35370390-G-T

Variant names:

• chr1-35370390-G-T
• rs745763874
• NM_005095.3:c.944G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005095.3(ZMYM4):​c.944G>T​(p.Gly315Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,345,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: ZMYM4 NM_005095.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.22
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38429588).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005095.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM4	NM_005095.3	MANE Select	c.944G>T	p.Gly315Val	missense	Exon 7 of 30	NP_005086.2
	ZMYM4	NM_001375653.1		c.953G>T	p.Gly318Val	missense	Exon 7 of 30	NP_001362582.1
	ZMYM4	NM_001350138.2		c.848G>T	p.Gly283Val	missense	Exon 8 of 31	NP_001337067.1	Q5VZL5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM4	ENST00000314607.11	TSL:2 MANE Select	c.944G>T	p.Gly315Val	missense	Exon 7 of 30	ENSP00000322915.6	Q5VZL5-1
	ZMYM4	ENST00000933225.1		c.944G>T	p.Gly315Val	missense	Exon 7 of 30	ENSP00000603284.1
	ZMYM4	ENST00000933226.1		c.944G>T	p.Gly315Val	missense	Exon 7 of 30	ENSP00000603285.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1345506 Hom.: 0 Cov.: 68 AF XY: 0.00000150 AC XY: 1 AN XY: 668414

African (AFR) AF: 0.00 AC: 0 AN: 27778

American (AMR) AF: 0.00 AC: 0 AN: 39708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23082

East Asian (EAS) AF: 0.00 AC: 0 AN: 27760

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5188

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040290

Other (OTH) AF: 0.00 AC: 0 AN: 53638

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.14
Sift	Benign	0.040	D
Sift4G	Benign	0.087	T
Polyphen		0.11	B
Vest4		0.74
MutPred		0.23		Loss of loop (P = 0.0603)
MVP		0.068
MPC		0.16
ClinPred		0.46	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.33
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745763874; hg19: chr1-35835991;