chr1-246987527-C-T

Variant names:

• chr1-246987527-C-T
• rs747743255
• NM_020394.5:c.988G>A

Variant summary

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

The NM_020394.5(ZNF695):​c.988G>A​(p.Gly330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,451,794 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ZNF695 NM_020394.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• 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=0.37995106).

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.988G>A	p.Gly330Ser	missense	Exon 4 of 4	NP_065127.5
	ZNF695	NM_001204221.2		c.390+598G>A		intron	N/A	NP_001191150.2	Q8IW36-1
	ZNF695	NR_037892.2		n.543+594G>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.988G>A	p.Gly330Ser	missense	Exon 4 of 4	ENSP00000341236.7	Q8IW36-4
	ZNF695	ENST00000487338.6	TSL:1	c.390+598G>A		intron	N/A	ENSP00000429736.1	Q8IW36-1
	ZNF695	ENST00000366504.6	TSL:1	n.394+594G>A		intron	N/A	ENSP00000355460.2	Q8IW36-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000210 AC: 5 AN: 237668 AF XY: 0.0000310

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000308

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1451794 Hom.: 0 Cov.: 37 AF XY: 0.0000139 AC XY: 10 AN XY: 721676

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.0000233 AC: 1 AN: 42910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25434

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.000166 AC: 14 AN: 84574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107688

Other (OTH) AF: 0.00 AC: 0 AN: 59920

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

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	0.29
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.2
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.19
Sift	Benign	0.052	T
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.11
MutPred		0.83		Gain of disorder (P = 0.0516)
MVP		0.17
MPC		0.21
ClinPred		0.85	D
GERP RS		0.64
Varity_R		0.21
gMVP		0.010
Mutation Taster		=82/18	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: rs747743255; hg19: chr1-247150829;