8-143296130-C-G

Variant names:

• chr8-143296130-C-G
• rs758885660
• NM_030895.3:c.455C>G

Variant summary

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

The NM_030895.3(ZNF696):​c.455C>G​(p.Pro152Arg) 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 1,457,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P152L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF696 NM_030895.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 publications found

Genes affected

ZNF696 (HGNC:25872): (zinc finger protein 696) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3090039).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030895.3. 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
	ZNF696	NM_030895.3	MANE Select	c.455C>G	p.Pro152Arg	missense	Exon 3 of 3	NP_112157.2	Q9H7X3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF696	ENST00000330143.8	TSL:1 MANE Select	c.455C>G	p.Pro152Arg	missense	Exon 3 of 3	ENSP00000328515.3	Q9H7X3
	ZNF696	ENST00000909971.1		c.455C>G	p.Pro152Arg	missense	Exon 3 of 3	ENSP00000580030.1
	ZNF696	ENST00000909972.1		c.455C>G	p.Pro152Arg	missense	Exon 3 of 3	ENSP00000580031.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457578 Hom.: 0 Cov.: 97 AF XY: 0.00 AC XY: 0 AN XY: 724944

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 85978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110698

Other (OTH) AF: 0.00 AC: 0 AN: 60256

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.4
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.43		Loss of ubiquitination at K151 (P = 0.0435)
MVP		0.31
MPC		1.1
ClinPred		0.93	D
GERP RS		2.2
Varity_R		0.34
gMVP		0.069
Mutation Taster		=85/15	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: rs758885660; hg19: chr8-144378300;