Variant chr1-247038239-C-G 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_033213.5(ZNF670):c.380G>C(p.Gly127Ala) 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF670
NM_033213.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.122

Variant links:

Genes affected

ZNF670 (HGNC:28167): (zinc finger protein 670) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF670 links:

ZNF670-ZNF695 (HGNC:):

ZNF670-ZNF695 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=0.22920945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF670	NM_033213.5 linkuse as main transcript	c.380G>C	p.Gly127Ala	missense_variant	4/4	ENST00000366503.3	NP_149990.1
ZNF670-ZNF695	NR_037894.2 linkuse as main transcript	n.219-38165G>C		intron_variant, non_coding_transcript_variant
ZNF670	NM_001204220.2 linkuse as main transcript	c.377G>C	p.Gly126Ala	missense_variant	4/4		NP_001191149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF670	ENST00000366503.3 linkuse as main transcript	c.380G>C	p.Gly127Ala	missense_variant	4/4	1	NM_033213.5	ENSP00000355459	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251356

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

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

Jun 03, 2022

The c.380G>C (p.G127A) alteration is located in exon 4 (coding exon 4) of the ZNF670 gene. This alteration results from a G to C substitution at nucleotide position 380, causing the glycine (G) at amino acid position 127 to be replaced by an alanine (A). 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

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.7

DANN

Benign

0.82

DEOGEN2

Benign

0.22

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.16

M_CAP

Benign

0.0019

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.058

Sift

Benign

0.038

Sift4G

Benign

0.062

Polyphen

0.97

Vest4

0.11

MutPred

0.54

Gain of catalytic residue at G127 (P = 0.0395);

MVP

0.36

MPC

0.13

ClinPred

0.30

GERP RS

-0.41

Varity_R

0.024

gMVP

0.023

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