Variant 1-248847282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000306562.8(ZNF672):c.8C>T(p.Ala3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,597,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF672
ENST00000306562.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366

Variant links:

Genes affected

ZNF672 (HGNC:26179): (zinc finger protein 672) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF672 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1394535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF672	NM_024836.3 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	4/4	ENST00000306562.8	NP_079112.1	Q499Z4
ZNF672	XM_005270336.3 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	4/4		XP_005270393.1	Q499Z4
ZNF672	XM_047430823.1 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	4/4		XP_047286779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF672	ENST00000306562.8 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	4/4	1	NM_024836.3	ENSP00000421915.1	Q499Z4
ZNF672	ENST00000428515.5 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	4/4	2		ENSP00000427021.1	D6RD56
ZNF672	ENST00000423362.1 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	4/4	5		ENSP00000426199.1	D6RH11
ZNF672	ENST00000505503.5 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	4/4	3		ENSP00000422534.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jun 29, 2023

The c.8C>T (p.A3V) alteration is located in exon 4 (coding exon 1) of the ZNF672 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the alanine (A) at amino acid position 3 to be replaced by a valine (V). 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

Benign

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.020

T;.;.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.47

T;.;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.084

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.63

N;D;N;N

REVEL

Benign

0.11

Sift

Benign

0.063

T;.;T;T

Sift4G

Benign

0.10

T;.;D;T

Polyphen

0.041

B;.;.;.

Vest4

0.11

MutPred

0.24

Loss of disorder (P = 0.0693);Loss of disorder (P = 0.0693);Loss of disorder (P = 0.0693);Loss of disorder (P = 0.0693);

MVP

0.15

MPC

0.72

ClinPred

0.14

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.046

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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