chr8-40626720-T-C

Variant names:

• chr8-40626720-T-C
• rs2722425
• NM_024645.3:c.578-45459A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024645.3(ZMAT4):​c.578-45459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,122 control chromosomes in the GnomAD database, including 47,806 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 0.78 (47806 hom., cov: 32)
• Consequence: ZMAT4 NM_024645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 26 publications found

Genes affected

ZMAT4 (HGNC:25844): (zinc finger matrin-type 4) Enables identical protein binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMAT4	NM_024645.3	c.578-45459A>G		intron_variant	Intron 5 of 6	ENST00000297737.11	NP_078921.1
ZMAT4	NM_001135731.2	c.350-45459A>G		intron_variant	Intron 4 of 5		NP_001129203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMAT4	ENST00000297737.11	c.578-45459A>G		intron_variant	Intron 5 of 6	2	NM_024645.3	ENSP00000297737.6
ZMAT4	ENST00000315769.11	c.350-45459A>G		intron_variant	Intron 4 of 5	1		ENSP00000319785.7
ZMAT4	ENST00000519406.5	c.578-45459A>G		intron_variant	Intron 5 of 5	3		ENSP00000428423.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119196 AN: 152004 Hom.: 47782 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.784 AC: 119269 AN: 152122 Hom.: 47806 Cov.: 32 AF XY: 0.782 AC XY: 58196 AN XY: 74388

African (AFR) AF: 0.620 AC: 25717 AN: 41466

American (AMR) AF: 0.735 AC: 11228 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2873 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3719 AN: 5160

South Asian (SAS) AF: 0.792 AC: 3819 AN: 4822

European-Finnish (FIN) AF: 0.877 AC: 9298 AN: 10598

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59959 AN: 68012

Other (OTH) AF: 0.811 AC: 1707 AN: 2106

Alfa AF: 0.840 Hom.: 173516

Bravo AF: 0.765

Asia WGS AF: 0.761 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.54
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2722425; hg19: chr8-40484239;