chr8-40697367-C-A

Position:

• chr8-40697367-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024645.3(ZMAT4):​c.227G>T​(p.Cys76Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMAT4 NM_024645.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.36

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]

ZMAT4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMAT4	NM_024645.3	c.227G>T	p.Cys76Phe	missense_variant	4/7	ENST00000297737.11	NP_078921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMAT4	ENST00000297737.11	c.227G>T	p.Cys76Phe	missense_variant	4/7	2	NM_024645.3	ENSP00000297737.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jul 10, 2024

The c.227G>T (p.C76F) alteration is located in exon 4 (coding exon 3) of the ZMAT4 gene. This alteration results from a G to T substitution at nucleotide position 227, causing the cysteine (C) at amino acid position 76 to be replaced by a phenylalanine (F). 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	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	.;T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	L;L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.42
Sift	Benign	0.90	T;T;T
Sift4G	Benign	0.62	T;T;.
Polyphen		0.066	B;D;.
Vest4		0.87
MutPred		0.48		Loss of catalytic residue at T78 (P = 0.0971);Loss of catalytic residue at T78 (P = 0.0971);Loss of catalytic residue at T78 (P = 0.0971);
MVP		0.28
MPC		2.1
ClinPred		0.96	D
GERP RS		6.2
Varity_R		0.53
gMVP		0.50

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: chr8-40554886;