Genetic Variant ZNF695:p.Gly386Asp (chr1-246987358-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020394.5(ZNF695):c.1157G>A(p.Gly386Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G386V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF695
NM_020394.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.177

Publications

0 publications found

Variant links:

Genes affected

ZNF695 (HGNC:30954): (zinc finger protein 695) 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]

ZNF695 links:

ZNF670-ZNF695 (HGNC:49200): (ZNF670-ZNF695 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 670 (ZNF670) and zinc finger protein 695 (ZNF695) genes on chromosome 1. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ZNF670-ZNF695 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23918149).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020394.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF695	NM_020394.5	MANE Select	c.1157G>A	p.Gly386Asp	missense	Exon 4 of 4	NP_065127.5
ZNF695	NM_001204221.2		c.390+767G>A		intron	N/A	NP_001191150.2	Q8IW36-1
ZNF695	NR_037892.2		n.543+763G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF695	ENST00000339986.8	TSL:1 MANE Select	c.1157G>A	p.Gly386Asp	missense	Exon 4 of 4	ENSP00000341236.7	Q8IW36-4
ZNF695	ENST00000487338.6	TSL:1	c.390+767G>A		intron	N/A	ENSP00000429736.1	Q8IW36-1
ZNF695	ENST00000366504.6	TSL:1	n.394+763G>A		intron	N/A	ENSP00000355460.2	Q8IW36-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111790

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.13

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.13

M_CAP

Benign

0.0039

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.18

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.087

Sift

Uncertain

0.024

Sift4G

Uncertain

0.0050

Polyphen

0.97

Vest4

0.18

MutPred

0.70

Gain of ubiquitination at K387 (P = 0.0725)

MVP

0.12

MPC

0.31

ClinPred

0.96

GERP RS

0.64

Varity_R

0.33

gMVP

0.0079

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over