1-246987632-G-C

Position:

• chr1-246987632-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020394.5(ZNF695):​c.883C>G​(p.Pro295Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF695 NM_020394.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.22

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]

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]

ZNF695 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28826606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF695	NM_020394.5	c.883C>G	p.Pro295Ala	missense_variant	4/4	ENST00000339986.8	NP_065127.5
ZNF695	NM_001204221.2	c.390+493C>G		intron_variant			NP_001191150.2
ZNF695	NR_037892.2	n.543+489C>G		intron_variant
ZNF670-ZNF695	NR_037894.2	n.573+489C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF695	ENST00000339986.8	c.883C>G	p.Pro295Ala	missense_variant	4/4	1	NM_020394.5	ENSP00000341236.7
ZNF670-ZNF695	ENST00000465049.6	n.358+489C>G		intron_variant		5		ENSP00000428213.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.883C>G (p.P295A) alteration is located in exon 4 (coding exon 4) of the ZNF695 gene. This alteration results from a C to G substitution at nucleotide position 883, causing the proline (P) at amino acid position 295 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	0.27
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.18
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.024	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Benign	0.22
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.18
MutPred		0.40		Gain of MoRF binding (P = 0.0994);
MVP		0.23
MPC		0.060
ClinPred		0.84	D
GERP RS		0.64
Varity_R		0.15
gMVP		0.0039

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.

Other links and lift over

hg19: chr1-247150934;