Variant 7-99560671-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000252713.9(ZNF655):c.112G>A(p.Asp38Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,924 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: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF655
ENST00000252713.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.679

Variant links:

Genes affected

ZNF655 (HGNC:30899): (zinc finger protein 655) This gene encodes a zinc finger protein. The zinc finger proteins are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ZNF655 links:

ENSG00000272647 (HGNC:):

ENSG00000272647 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.06532693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF655	NM_138494.3 linkuse as main transcript	c.112G>A	p.Asp38Asn	missense_variant	2/3	ENST00000252713.9	NP_612503.1	Q8N720-1Q68DU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF655	ENST00000252713.9 linkuse as main transcript	c.112G>A	p.Asp38Asn	missense_variant	2/3	1	NM_138494.3	ENSP00000252713.4		Q8N720-1
ENSG00000272647	ENST00000455905.1 linkuse as main transcript	n.112G>A		non_coding_transcript_exon_variant	2/6	3		ENSP00000401282.1		F8WEM9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152154

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251276

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

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

AF:

0.00000616

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Apr 25, 2022

The c.112G>A (p.D38N) alteration is located in exon 2 (coding exon 1) of the ZNF655 gene. This alteration results from a G to A substitution at nucleotide position 112, causing the aspartic acid (D) at amino acid position 38 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;.;T;.;T;T;.;T;.;T;T;T;.;.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.88

D;D;D;D;.;.;D;.;.;D;D;D;D;.;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.065

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.;.;M;.;.;.;M;.;.;.;M;M;M

MutationTaster

Benign

0.99

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

N;D;.;D;N;D;D;D;N;N;N;N;N;D;N

REVEL

Benign

0.029

Sift

Uncertain

0.0030

D;D;.;D;T;D;D;D;T;T;T;T;T;D;T

Sift4G

Benign

0.20

T;D;D;D;T;D;D;D;T;D;D;D;T;D;T

Polyphen

0.99

D;.;.;.;B;.;.;.;B;.;.;.;B;.;B

Vest4

0.25

MutPred

0.39

Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);Loss of phosphorylation at T37 (P = 0.1077);

MVP

0.061

MPC

0.24

ClinPred

0.49

GERP RS

1.5

Varity_R

0.029

gMVP

0.10

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