rs1823643

Variant names:

• chr8-40657569-C-T
• rs1823643
• NM_024645.3:c.577+17135G>A

Variant summary

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

The NM_024645.3(ZMAT4):​c.577+17135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,066 control chromosomes in the GnomAD database, including 55,110 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 0.84 (55110 hom., cov: 32)
• Consequence: ZMAT4 NM_024645.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 3 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 = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMAT4	NM_024645.3	c.577+17135G>A		intron_variant	Intron 5 of 6	ENST00000297737.11	NP_078921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMAT4	ENST00000297737.11	c.577+17135G>A		intron_variant	Intron 5 of 6	2	NM_024645.3	ENSP00000297737.6
ZMAT4	ENST00000315769.11	c.349+39676G>A		intron_variant	Intron 4 of 5	1		ENSP00000319785.7
ZMAT4	ENST00000519406.5	c.577+17135G>A		intron_variant	Intron 5 of 5	3		ENSP00000428423.1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128339 AN: 151948 Hom.: 55073 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.845 AC: 128433 AN: 152066 Hom.: 55110 Cov.: 32 AF XY: 0.846 AC XY: 62907 AN XY: 74342

African (AFR) AF: 0.678 AC: 28088 AN: 41414

American (AMR) AF: 0.903 AC: 13785 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2972 AN: 3472

East Asian (EAS) AF: 0.809 AC: 4174 AN: 5162

South Asian (SAS) AF: 0.899 AC: 4331 AN: 4820

European-Finnish (FIN) AF: 0.911 AC: 9651 AN: 10594

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62603 AN: 68014

Other (OTH) AF: 0.866 AC: 1830 AN: 2112

Alfa AF: 0.896 Hom.: 140450

Bravo AF: 0.836

Asia WGS AF: 0.846 AC: 2931 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		0.16
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: rs1823643; hg19: chr8-40515088;