8-143296105-C-G

Variant names:

• chr8-143296105-C-G
• rs1261333868
• NM_030895.3:c.430C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030895.3(ZNF696):​c.430C>G​(p.Arg144Gly) 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. 14/22 in silico tools predict 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. R144Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: ZNF696 NM_030895.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14984012).

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.430C>G	p.Arg144Gly	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.430C>G	p.Arg144Gly	missense	Exon 3 of 3	ENSP00000328515.3	Q9H7X3
	ZNF696	ENST00000909971.1		c.430C>G	p.Arg144Gly	missense	Exon 3 of 3	ENSP00000580030.1
	ZNF696	ENST00000909972.1		c.430C>G	p.Arg144Gly	missense	Exon 3 of 3	ENSP00000580031.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 95

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.4
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.081
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.11	T
Polyphen		0.96	D
Vest4		0.063
MutPred		0.36		Gain of ubiquitination at K142 (P = 0.0231)
MVP		0.20
MPC		0.87
ClinPred		0.94	D
GERP RS		2.4
Varity_R		0.29
gMVP		0.15
Mutation Taster		=94/6	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: rs1261333868; hg19: chr8-144378275;