Variant 7-64068904-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001159522.3(ZNF727):c.17T>C(p.Phe6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,447,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ZNF727
NM_001159522.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

ZNF727 (HGNC:22785): (zinc finger protein 727) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF727 links:

ZNF727 (HGNC:):

ZNF727 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF727	NM_001159522.3 linkuse as main transcript	c.17T>C	p.Phe6Ser	missense_variant	2/4	ENST00000456806.3	NP_001152994.1	A8MUV8
ZNF727	XM_017012225.3 linkuse as main transcript	c.17T>C	p.Phe6Ser	missense_variant	2/3		XP_016867714.1
ZNF727	XR_242241.4 linkuse as main transcript	n.205T>C		non_coding_transcript_exon_variant	2/5
ZNF727	XR_927469.2 linkuse as main transcript	n.205T>C		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF727	ENST00000456806.3 linkuse as main transcript	c.17T>C	p.Phe6Ser	missense_variant	2/4	4	NM_001159522.3	ENSP00000485448.1		A8MUV8
ENSG00000285544	ENST00000647787.1 linkuse as main transcript	n.196+23280T>C		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000434

AC:

AN:

230534

Hom.:

AF XY:

0.00000800

AC XY:

AN XY:

124952

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000595

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1447674

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000516

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.17T>C (p.F6S) alteration is located in exon 2 (coding exon 2) of the ZNF727 gene. This alteration results from a T to C substitution at nucleotide position 17, causing the phenylalanine (F) at amino acid position 6 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.080

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.63

M_CAP

Benign

0.0028

MetaRNN

Pathogenic

0.91

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

4.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.56

MutPred

0.82

Gain of disorder (P = 0.003);

MVP

0.25

ClinPred

0.76

GERP RS

0.15

Varity_R

0.088

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over