8-40674858-T-A

Position:

• chr8-40674858-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMAT4	NM_024645.3	c.423A>T	p.Arg141Ser	missense_variant	5/7	ENST00000297737.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMAT4	ENST00000297737.11	c.423A>T	p.Arg141Ser	missense_variant	5/7	2	NM_024645.3	P1
ZMAT4	ENST00000315769.11	c.349+22387A>T		intron_variant		1
ZMAT4	ENST00000519406.5	c.423A>T	p.Arg141Ser	missense_variant	5/6	3
ZMAT4	ENST00000519806.1	n.167A>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.423A>T (p.R141S) alteration is located in exon 5 (coding exon 4) of the ZMAT4 gene. This alteration results from a A to T substitution at nucleotide position 423, causing the arginine (R) at amino acid position 141 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.14
Sift	Benign	0.73	T;T
Sift4G	Benign	0.60	T;.
Polyphen		0.48	P;.
Vest4		0.67
MutPred		0.37		Loss of stability (P = 0.0597);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-40532377;