dbSNP rs201694502: ZNF695:p.Thr340Ile (chr1-246987496-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_020394.5(ZNF695):c.1019C>T(p.Thr340Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,914 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. 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. T340S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF695
NM_020394.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

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 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=0.106731266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF695	NM_020394.5 link	c.1019C>T	p.Thr340Ile	missense_variant	Exon 4 of 4	ENST00000339986.8	NP_065127.5
ZNF695	NM_001204221.2 link	c.390+629C>T		intron_variant	Intron 4 of 5		NP_001191150.2	Q8IW36-1
ZNF695	NR_037892.2 link	n.543+625C>T		intron_variant	Intron 4 of 5
ZNF670-ZNF695	NR_037894.2 link	n.573+625C>T		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF695	ENST00000339986.8 link	c.1019C>T	p.Thr340Ile	missense_variant	Exon 4 of 4	1	NM_020394.5	ENSP00000341236.7		Q8IW36-4
ZNF670-ZNF695	ENST00000465049.6 link	n.358+625C>T		intron_variant	Intron 4 of 6	5		ENSP00000428213.1		F2Z2N8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456914

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724682

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.060

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0

LIST_S2

Benign

0.65

M_CAP

Benign

0.0015

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.44

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.051

Sift

Benign

0.065

Sift4G

Benign

0.21

Polyphen

0.70

Vest4

0.031

MutPred

0.50

Loss of disorder (P = 0.049);

MVP

0.11

MPC

0.11

ClinPred

0.18

GERP RS

0.64

Varity_R

0.11

gMVP

0.0075

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

Computational scores

Splicing

Publications

Other links and lift over