Variant chr1-248847743-G-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 NM_024836.3(ZNF672):c.469G>T(p.Asp157Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000753 in 1,328,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

ZNF672
NM_024836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24

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:

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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=0.07311094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF672	NM_024836.3 linkuse as main transcript	c.469G>T	p.Asp157Tyr	missense_variant	4/4	ENST00000306562.8
ZNF672	XM_005270336.3 linkuse as main transcript	c.469G>T	p.Asp157Tyr	missense_variant	4/4
ZNF672	XM_047430823.1 linkuse as main transcript	c.469G>T	p.Asp157Tyr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF672	ENST00000306562.8 linkuse as main transcript	c.469G>T	p.Asp157Tyr	missense_variant	4/4	1	NM_024836.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.53e-7

AC:

AN:

1328122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648704

show subpopulations

Gnomad4 AFR exome

AF:

0.0000337

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 02, 2022

The c.469G>T (p.D157Y) alteration is located in exon 4 (coding exon 1) of the ZNF672 gene. This alteration results from a G to T substitution at nucleotide position 469, causing the aspartic acid (D) at amino acid position 157 to be replaced by a tyrosine (Y). 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

0.18

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.98

DANN

Benign

0.72

DEOGEN2

Benign

0.041

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.25

M_CAP

Benign

0.0084

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.23

REVEL

Benign

0.024

Sift

Benign

0.16

Sift4G

Pathogenic

0.0

Polyphen

0.10

Vest4

0.12

MutPred

0.23

Gain of catalytic residue at D157 (P = 0.0348);

MVP

0.12

MPC

0.96

ClinPred

0.11

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.24

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over