chr8-40674858-T-A

Variant names:

• chr8-40674858-T-A
• NM_024645.3:c.423A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024645.3(ZMAT4):​c.423A>T​(p.Arg141Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMAT4 NM_024645.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.897
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15060687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024645.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT4	NM_024645.3	MANE Select	c.423A>T	p.Arg141Ser	missense	Exon 5 of 7	NP_078921.1	Q9H898-1
	ZMAT4	NM_001135731.2		c.349+22387A>T		intron	N/A	NP_001129203.1	Q9H898-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT4	ENST00000297737.11	TSL:2 MANE Select	c.423A>T	p.Arg141Ser	missense	Exon 5 of 7	ENSP00000297737.6	Q9H898-1
	ZMAT4	ENST00000315769.11	TSL:1	c.349+22387A>T		intron	N/A	ENSP00000319785.7	Q9H898-2
	ZMAT4	ENST00000958182.1		c.423A>T	p.Arg141Ser	missense	Exon 5 of 7	ENSP00000628241.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.00076	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.067
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.90
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.73	T
Sift4G	Benign	0.60	T
Polyphen		0.48	P
Vest4		0.67
MutPred		0.37		Loss of stability (P = 0.0597)
MVP		0.32
MPC		1.0
ClinPred		0.72	D
GERP RS		5.9
Varity_R		0.19
gMVP		0.42
Mutation Taster		=32/68	disease causing

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

hg19: chr8-40532377;