NM_020394.5:c.1157G>T

Variant names:

• chr1-246987358-C-A
• rs1159304444
• NM_020394.5:c.1157G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020394.5(ZNF695):​c.1157G>T​(p.Gly386Val) 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. 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: 0.177
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39809343).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF695	NM_020394.5	MANE Select	c.1157G>T	p.Gly386Val	missense	Exon 4 of 4	NP_065127.5
	ZNF695	NM_001204221.2		c.390+767G>T		intron	N/A	NP_001191150.2	Q8IW36-1
	ZNF695	NR_037892.2		n.543+763G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF695	ENST00000339986.8	TSL:1 MANE Select	c.1157G>T	p.Gly386Val	missense	Exon 4 of 4	ENSP00000341236.7	Q8IW36-4
	ZNF695	ENST00000487338.6	TSL:1	c.390+767G>T		intron	N/A	ENSP00000429736.1	Q8IW36-1
	ZNF695	ENST00000366504.6	TSL:1	n.394+763G>T		intron	N/A	ENSP00000355460.2	Q8IW36-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.000060	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.18
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.72		Loss of disorder (P = 0.069)
MVP		0.28
MPC		0.31
ClinPred		0.99	D
GERP RS		0.64
Varity_R		0.72
gMVP		0.024
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1159304444; hg19: chr1-247150660;