19-55614470-G-C

Variant names:

• chr19-55614470-G-C
• rs1265369190
• NM_001195605.2:c.852G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001195605.2(ZNF865):​c.852G>C​(p.Pro284Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P284P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF865 NM_001195605.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 0 publications found

Genes affected

ZNF865 (HGNC:38705): (zinc finger protein 865) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-0.972 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195605.2. 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
	ZNF865	NM_001195605.2	MANE Select	c.852G>C	p.Pro284Pro	synonymous	Exon 2 of 2	NP_001182534.1	P0CJ78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF865	ENST00000568956.2	TSL:2 MANE Select	c.852G>C	p.Pro284Pro	synonymous	Exon 2 of 2	ENSP00000457715.1	P0CJ78
	ZNF865	ENST00000870148.1		c.852G>C	p.Pro284Pro	synonymous	Exon 3 of 3	ENSP00000540207.1
	ZNF865	ENST00000870149.1		c.852G>C	p.Pro284Pro	synonymous	Exon 2 of 2	ENSP00000540208.1

Frequencies

GnomAD3 genomes AF: 0.0000357 AC: 5 AN: 139932 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000255

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000313

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000437 AC: 45 AN: 1030356 Hom.: 0 Cov.: 33 AF XY: 0.0000374 AC XY: 19 AN XY: 508284

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

African (AFR) AF: 0.000143 AC: 3 AN: 20912

American (AMR) AF: 0.00 AC: 0 AN: 16448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16046

East Asian (EAS) AF: 0.00 AC: 0 AN: 19916

South Asian (SAS) AF: 0.00 AC: 0 AN: 59044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2866

European-Non Finnish (NFE) AF: 0.0000467 AC: 39 AN: 835534

Other (OTH) AF: 0.0000729 AC: 3 AN: 41144

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000357 AC: 5 AN: 140058 Hom.: 0 Cov.: 31 AF XY: 0.0000294 AC XY: 2 AN XY: 68130

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

African (AFR) AF: 0.0000516 AC: 2 AN: 38790

American (AMR) AF: 0.00 AC: 0 AN: 14276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3332

East Asian (EAS) AF: 0.00 AC: 0 AN: 4098

South Asian (SAS) AF: 0.000254 AC: 1 AN: 3938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.0000313 AC: 2 AN: 63942

Other (OTH) AF: 0.00 AC: 0 AN: 1994

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.82
DANN	Benign	0.84
PhyloP100		-0.97
Mutation Taster		=100/0	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: rs1265369190; hg19: chr19-56125836;