8-144807368-C-A

Variant names:

• chr8-144807368-C-A
• rs778826784
• NM_213605.3:c.452C>A

Variant summary

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

The NM_213605.3(ZNF517):​c.452C>A​(p.Pro151His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P151L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF517 NM_213605.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 0 publications found

Genes affected

ZNF517 (HGNC:27984): (zinc finger protein 517) 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058977902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213605.3. 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
	ZNF517	NM_213605.3	MANE Select	c.452C>A	p.Pro151His	missense	Exon 5 of 5	NP_998770.2	Q6ZMY9
	ZNF517	NM_001384904.1		c.452C>A	p.Pro151His	missense	Exon 5 of 5	NP_001371833.1	Q6ZMY9
	ZNF517	NM_001384905.1		c.452C>A	p.Pro151His	missense	Exon 6 of 6	NP_001371834.1	Q6ZMY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF517	ENST00000359971.4	TSL:4 MANE Select	c.452C>A	p.Pro151His	missense	Exon 5 of 5	ENSP00000353058.3	Q6ZMY9
	ZNF517	ENST00000529429.5	TSL:1	c.350C>A	p.Pro117His	missense	Exon 3 of 3	ENSP00000432025.1	H0YCN3
	ZNF517	ENST00000525105.5	TSL:1	c.275-2738C>A		intron	N/A	ENSP00000433299.1	G3V191

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1403064 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 692878

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31714

American (AMR) AF: 0.00 AC: 0 AN: 36078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25018

East Asian (EAS) AF: 0.00 AC: 0 AN: 35934

South Asian (SAS) AF: 0.00 AC: 0 AN: 80392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1081316

Other (OTH) AF: 0.0000172 AC: 1 AN: 58188

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.49
DANN	Benign	0.51
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.023
Sift	Benign	0.43	T
Sift4G	Benign	0.13	T
Polyphen		0.010	B
Vest4		0.14
MVP		0.095
MPC		0.93
ClinPred		0.089	T
GERP RS		-1.8
Varity_R		0.063
gMVP		0.077
Mutation Taster		=98/2	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: rs778826784; hg19: chr8-146032753;