19-55614597-G-A

Position:

• chr19-55614597-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195605.2(ZNF865):​c.979G>A​(p.Ala327Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000855 in 1,521,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: ZNF865 NM_001195605.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053897947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF865	NM_001195605.2	c.979G>A	p.Ala327Thr	missense_variant	2/2	ENST00000568956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF865	ENST00000568956.2	c.979G>A	p.Ala327Thr	missense_variant	2/2	2	NM_001195605.2	P1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151602 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000584 AC: 8 AN: 1369550 Hom.: 0 Cov.: 38 AF XY: 0.00000592 AC XY: 4 AN XY: 675540

Gnomad4 AFR exome AF: 0.0000328

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000653

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000330 AC: 5 AN: 151602 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74016

Gnomad4 AFR AF: 0.0000726

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.48
DANN	Benign	0.78
DEOGEN2	Benign	0.0040	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.34	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.054	T
MutationAssessor	Benign	0.20	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.36	N
Sift	Benign	0.70	T
Sift4G	Benign	0.41	T
Vest4		0.062
MVP		0.20
GERP RS		-5.7
Varity_R		0.022
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs1305436518; hg19: chr19-56125963; COSMIC: COSV73830400; COSMIC: COSV73830400;