X-101883920-G-C

Variant names:

• chrX-101883920-G-C
• rs768283759
• NM_001394560.1:c.1678C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001394560.1(ZMAT1):​c.1678C>G​(p.Gln560Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,097,340 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q560K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 2 publications found

Genes affected

ZMAT1 (HGNC:29377): (zinc finger matrin-type 1) This gene encodes a protein containing Cys2-His2 (C2H2)-type zinc fingers, which are similar to those found in the nuclear matrix protein matrin 3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09707898).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394560.1. 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
	ZMAT1	NM_001394560.1	MANE Select	c.1678C>G	p.Gln560Glu	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
	ZMAT1	NM_001011657.4		c.1507C>G	p.Gln503Glu	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
	ZMAT1	NM_001282400.2		c.994C>G	p.Gln332Glu	missense	Exon 10 of 10	NP_001269329.1	Q5H9K5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT1	ENST00000651725.2	MANE Select	c.1678C>G	p.Gln560Glu	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
	ZMAT1	ENST00000372782.4	TSL:1	c.1507C>G	p.Gln503Glu	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
	ZMAT1	ENST00000878190.1		c.1747C>G	p.Gln583Glu	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1097340 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 2 AN XY: 363054

African (AFR) AF: 0.00 AC: 0 AN: 26359

American (AMR) AF: 0.00 AC: 0 AN: 35066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19336

East Asian (EAS) AF: 0.00 AC: 0 AN: 30182

South Asian (SAS) AF: 0.00 AC: 0 AN: 54077

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 841730

Other (OTH) AF: 0.00 AC: 0 AN: 46040

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.65	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.020
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.021	D
Vest4		0.094
MutPred		0.11		Gain of phosphorylation at S500 (P = 0.1056)
MVP		0.44
MPC		0.10
ClinPred		0.22	T
GERP RS		3.5
gMVP		0.23
Mutation Taster		=90/10	polymorphism

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: rs768283759; hg19: chrX-101138892; COSMIC: COSV107475526; COSMIC: COSV107475526;