chrX-101884057-C-T

Variant names:

• chrX-101884057-C-T
• NM_001394560.1:c.1541G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001394560.1(ZMAT1):​c.1541G>A​(p.Ser514Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,096,505 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: ZMAT1 NM_001394560.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.33
• Publications: 0 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059556305).
• BP6: Variant X-101884057-C-T is Benign according to our data. Variant chrX-101884057-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3473957.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1541G>A	p.Ser514Asn	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
	ZMAT1	NM_001011657.4		c.1370G>A	p.Ser457Asn	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
	ZMAT1	NM_001282400.2		c.857G>A	p.Ser286Asn	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.1541G>A	p.Ser514Asn	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
	ZMAT1	ENST00000372782.4	TSL:1	c.1370G>A	p.Ser457Asn	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
	ZMAT1	ENST00000878190.1		c.1610G>A	p.Ser537Asn	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096505 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1 AN XY: 362529

African (AFR) AF: 0.00 AC: 0 AN: 26364

American (AMR) AF: 0.00 AC: 0 AN: 35110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19360

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54113

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841883

Other (OTH) AF: 0.00 AC: 0 AN: 46056

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.080
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.0030
DANN	Benign	0.58
FATHMM_MKL	Benign	0.0085	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.0090
Sift	Benign	0.45	T
Sift4G	Benign	0.24	T
Vest4		0.025
MutPred		0.23		Gain of helix (P = 0.027)
MVP		0.30
MPC		0.084
ClinPred		0.13	T
GERP RS		-7.8
gMVP		0.065
Mutation Taster		=98/2	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

hg19: chrX-101139029;