chr1-246987353-C-T

Variant names:

• chr1-246987353-C-T
• NM_020394.5:c.1162G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020394.5(ZNF695):​c.1162G>A​(p.Ala388Thr) 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. 15/22 in silico tools predict 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: -1.51
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0514673).

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.1162G>A	p.Ala388Thr	missense	Exon 4 of 4	NP_065127.5
	ZNF695	NM_001204221.2		c.390+772G>A		intron	N/A	NP_001191150.2	Q8IW36-1
	ZNF695	NR_037892.2		n.543+768G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF695	ENST00000339986.8	TSL:1 MANE Select	c.1162G>A	p.Ala388Thr	missense	Exon 4 of 4	ENSP00000341236.7	Q8IW36-4
	ZNF695	ENST00000487338.6	TSL:1	c.390+772G>A		intron	N/A	ENSP00000429736.1	Q8IW36-1
	ZNF695	ENST00000366504.6	TSL:1	n.394+768G>A		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	Benign	0.21
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-1.5
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.029
Sift	Benign	0.11	T
Sift4G	Benign	0.096	T
Polyphen		0.048	B
Vest4		0.051
MutPred		0.65		Loss of catalytic residue at A388 (P = 0.0436)
MVP		0.061
MPC		0.24
ClinPred		0.30	T
GERP RS		-0.87
Varity_R		0.094
gMVP		0.0039
Mutation Taster		=100/0	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

hg19: chr1-247150655;