22-29736799-T-C

Position:

• chr22-29736799-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003692.2(ZMAT5):​c.383+1531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 128,846 control chromosomes in the GnomAD database, including 15,893 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (15893 hom., cov: 22)
• Consequence: ZMAT5 NM_001003692.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.65

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.12).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMAT5	NM_001003692.2	c.383+1531A>G		intron_variant		ENST00000344318.4	NP_001003692.1
ZMAT5	NM_001318129.2	c.383+1531A>G		intron_variant			NP_001305058.1
ZMAT5	NM_019103.3	c.383+1531A>G		intron_variant			NP_061976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMAT5	ENST00000344318.4	c.383+1531A>G		intron_variant		1	NM_001003692.2	ENSP00000344241	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 67393 AN: 128780 Hom.: 15884 Cov.: 22

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.534

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 67428 AN: 128846 Hom.: 15893 Cov.: 22 AF XY: 0.514 AC XY: 31736 AN XY: 61696

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.539

Alfa AF: 0.312 Hom.: 689

Bravo AF: 0.469

Asia WGS AF: 0.409 AC: 1424 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.015
DANN	Benign	0.063

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

LitVar

Other links and lift over

dbSNP: rs131259; hg19: chr22-30132788;