NM_001099220.3:c.409C>A

Variant names:

• chr7-149847902-C-A
• rs573806805
• NM_001099220.3:c.409C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001099220.3(ZNF862):​c.409C>A​(p.Arg137Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,818 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF862 NM_001099220.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

Genes affected

ZNF862 (HGNC:34519): (zinc finger protein 862) Predicted to enable metal ion binding activity and protein dimerization 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=1.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099220.3. 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
	ZNF862	NM_001099220.3	MANE Select	c.409C>A	p.Arg137Arg	synonymous	Exon 4 of 8	NP_001092690.1	O60290-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF862	ENST00000223210.5	TSL:5 MANE Select	c.409C>A	p.Arg137Arg	synonymous	Exon 4 of 8	ENSP00000223210.4	O60290-1
	ZNF862	ENST00000460379.1	TSL:4	c.157C>A	p.Arg53Arg	synonymous	Exon 4 of 4	ENSP00000417450.1	C9JB70
	ZNF862	ENST00000488265.1	TSL:3	n.-225C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454818 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723056

⚠️ 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: 33304

American (AMR) AF: 0.00 AC: 0 AN: 43468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39352

South Asian (SAS) AF: 0.00 AC: 0 AN: 85250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108530

Other (OTH) AF: 0.00 AC: 0 AN: 60142

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	5.8
DANN	Benign	0.55
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs573806805; hg19: chr7-149544991;