chr20-49247452-C-T

Variant names:

• chr20-49247452-C-T
• NM_021035.3:c.5572G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_021035.3(ZNFX1):​c.5572G>A​(p.Gly1858Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNFX1 NM_021035.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.672

Genes affected

ZNFX1 (HGNC:29271): (zinc finger NFX1-type containing 1) Enables RNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA. Predicted to be part of nuclear RNA-directed RNA polymerase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07349515).
• BP6: Variant 20-49247452-C-T is Benign according to our data. Variant chr20-49247452-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3199090.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNFX1	NM_021035.3	c.5572G>A	p.Gly1858Ser	missense_variant	Exon 14 of 14	ENST00000396105.6	NP_066363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNFX1	ENST00000396105.6	c.5572G>A	p.Gly1858Ser	missense_variant	Exon 14 of 14	1	NM_021035.3	ENSP00000379412.1
ZNFX1	ENST00000371754.8	c.3312+4075G>A		intron_variant	Intron 13 of 14	1		ENSP00000360819.4
ZNFX1	ENST00000371752.5	c.5572G>A	p.Gly1858Ser	missense_variant	Exon 14 of 14	5		ENSP00000360817.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Oct 13, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.39	T;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.073	T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.20	T;T
Sift4G	Uncertain	0.057	T;T
Polyphen		0.0020	B;B
Vest4		0.083
MutPred		0.41		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.21
MPC		0.39
ClinPred		0.058	T
GERP RS		-4.1
Varity_R		0.086
gMVP		0.47

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: chr20-47863989;