19-57253231-C-T

Variant names:

• chr19-57253231-C-T
• rs61736510
• NM_001023563.4:c.412C>T

Variant summary

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

The NM_001023563.4(ZNF805):​c.412C>T​(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,556,910 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: ZNF805 NM_001023563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.79
• Publications: 0 publications found

Genes affected

ZNF805 (HGNC:23272): (zinc finger protein 805) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific 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 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=0.05675313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023563.4. 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
	ZNF805	NM_001023563.4	MANE Select	c.412C>T	p.Arg138Cys	missense	Exon 4 of 4	NP_001018857.2	Q5CZA5-1
	ZNF805	NM_001145078.2		c.13C>T	p.Arg5Cys	missense	Exon 3 of 3	NP_001138550.1	Q5CZA5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF805	ENST00000414468.3	TSL:5 MANE Select	c.412C>T	p.Arg138Cys	missense	Exon 4 of 4	ENSP00000412999.1	Q5CZA5-1
	ZNF805	ENST00000354309.4	TSL:5	c.13C>T	p.Arg5Cys	missense	Exon 3 of 3	ENSP00000365414.2	Q5CZA5-2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000368 AC: 6 AN: 162850 AF XY: 0.0000578

Gnomad AFR exome AF: 0.000113

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000455

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.0000164 AC: 23 AN: 1404730 Hom.: 0 Cov.: 30 AF XY: 0.0000159 AC XY: 11 AN XY: 693766

African (AFR) AF: 0.00 AC: 0 AN: 31722

American (AMR) AF: 0.00 AC: 0 AN: 35480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24894

East Asian (EAS) AF: 0.00 AC: 0 AN: 36870

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.0000166 AC: 18 AN: 1082588

Other (OTH) AF: 0.0000515 AC: 3 AN: 58236

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74350

African (AFR) AF: 0.0000724 AC: 3 AN: 41432

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000761 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000256 AC: 3

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	Benign	0.065
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.59
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.8
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.0070
Sift	Benign	0.17	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.071
MVP		0.043
MPC		0.33
ClinPred		0.011	T
GERP RS		-1.9
Varity_R		0.046
gMVP		0.064
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: rs61736510; hg19: chr19-57764599; COSMIC: COSV100846119;