22-29742469-T-C

Position:

• chr22-29742469-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003692.2(ZMAT5):​c.139A>G​(p.Ile47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMAT5 NM_001003692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16

Genes affected

ZMAT5 (HGNC:28046): (zinc finger matrin-type 5) Predicted to enable zinc ion binding activity. Predicted to be involved in RNA splicing. Located in nucleoplasm. Part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10385078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMAT5	NM_001003692.2	c.139A>G	p.Ile47Val	missense_variant	3/6	ENST00000344318.4	NP_001003692.1
ZMAT5	NM_001318129.2	c.139A>G	p.Ile47Val	missense_variant	3/6		NP_001305058.1
ZMAT5	NM_019103.3	c.139A>G	p.Ile47Val	missense_variant	4/7		NP_061976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMAT5	ENST00000344318.4	c.139A>G	p.Ile47Val	missense_variant	3/6	1	NM_001003692.2	ENSP00000344241	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 27, 2022

The c.139A>G (p.I47V) alteration is located in exon 4 (coding exon 2) of the ZMAT5 gene. This alteration results from a A to G substitution at nucleotide position 139, causing the isoleucine (I) at amino acid position 47 to be replaced by a valine (V). 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	0.067
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.095
Sift	Benign	0.31	T
Sift4G	Benign	0.51	T
Polyphen		0.0030	B
Vest4		0.20
MutPred		0.39		Gain of helix (P = 0.0022);
MVP		0.061
ClinPred		0.34	T
GERP RS		4.4
Varity_R		0.042
gMVP		0.46

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: chr22-30138458;