chr8-143296325-C-T

Variant names:

• chr8-143296325-C-T
• rs200159338
• NM_030895.3:c.650C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030895.3(ZNF696):​c.650C>T​(p.Ala217Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,596,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 35)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ZNF696 NM_030895.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.694
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038103938).

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.650C>T	p.Ala217Val	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.650C>T	p.Ala217Val	missense	Exon 3 of 3	ENSP00000328515.3	Q9H7X3
	ZNF696	ENST00000909971.1		c.650C>T	p.Ala217Val	missense	Exon 3 of 3	ENSP00000580030.1
	ZNF696	ENST00000909972.1		c.650C>T	p.Ala217Val	missense	Exon 3 of 3	ENSP00000580031.1

Frequencies

GnomAD3 genomes AF: 0.000198 AC: 30 AN: 151804 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000309 AC: 68 AN: 220318 AF XY: 0.000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000824

Gnomad NFE exome AF: 0.000562

Gnomad OTH exome AF: 0.000180

GnomAD4 exome AF: 0.000173 AC: 250 AN: 1444512 Hom.: 0 Cov.: 97 AF XY: 0.000180 AC XY: 129 AN XY: 718390

African (AFR) AF: 0.00 AC: 0 AN: 33174

American (AMR) AF: 0.00 AC: 0 AN: 43810

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25758

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 85530

European-Finnish (FIN) AF: 0.00105 AC: 46 AN: 43984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.000179 AC: 198 AN: 1107276

Other (OTH) AF: 0.0000836 AC: 5 AN: 59830

GnomAD4 genome AF: 0.000198 AC: 30 AN: 151804 Hom.: 0 Cov.: 35 AF XY: 0.000229 AC XY: 17 AN XY: 74156

African (AFR) AF: 0.0000242 AC: 1 AN: 41302

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000946 AC: 10 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67916

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.000259 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.000439 AC: 52

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.69
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.0080
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.044	D
Polyphen		0.82	P
Vest4		0.059
MVP		0.20
MPC		0.94
ClinPred		0.18	T
GERP RS		0.59
Varity_R		0.20
gMVP		0.024
Mutation Taster		=99/1	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: rs200159338; hg19: chr8-144378495;