22-29736799-T-G

Variant names:

• chr22-29736799-T-G
• rs131259
• NM_001003692.2:c.383+1531A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003692.2(ZMAT5):​c.383+1531A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00027 (0 hom., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: ZMAT5 NM_001003692.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.65
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.11).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003692.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT5	NM_001003692.2	MANE Select	c.383+1531A>C		intron	N/A	NP_001003692.1
	ZMAT5	NM_001318129.2		c.383+1531A>C		intron	N/A	NP_001305058.1
	ZMAT5	NM_019103.3		c.383+1531A>C		intron	N/A	NP_061976.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT5	ENST00000344318.4	TSL:1 MANE Select	c.383+1531A>C		intron	N/A	ENSP00000344241.3

Frequencies

GnomAD3 genomes AF: 0.000271 AC: 35 AN: 129046 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000581

Gnomad FIN AF: 0.000664

Gnomad MID AF: 0.00476

Gnomad NFE AF: 0.0000490

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000271 AC: 35 AN: 129046 Hom.: 0 Cov.: 22 AF XY: 0.000372 AC XY: 23 AN XY: 61750

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000583 AC: 20 AN: 34322

American (AMR) AF: 0.000334 AC: 4 AN: 11992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3186

East Asian (EAS) AF: 0.00 AC: 0 AN: 4640

South Asian (SAS) AF: 0.000581 AC: 2 AN: 3444

European-Finnish (FIN) AF: 0.000664 AC: 5 AN: 7532

Middle Eastern (MID) AF: 0.00476 AC: 1 AN: 210

European-Non Finnish (NFE) AF: 0.0000490 AC: 3 AN: 61166

Other (OTH) AF: 0.00 AC: 0 AN: 1758

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.014
DANN	Benign	0.087
PhyloP100		-4.7

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

Other links and lift over

dbSNP: rs131259; hg19: chr22-30132788;