chr7-149847936-C-T

Variant names:

• chr7-149847936-C-T
• rs201261199
• NM_001099220.3:c.443C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099220.3(ZNF862):​c.443C>T​(p.Pro148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,606,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: ZNF862 NM_001099220.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.25
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034695864).

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.443C>T	p.Pro148Leu	missense	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.443C>T	p.Pro148Leu	missense	Exon 4 of 8	ENSP00000223210.4	O60290-1
	ZNF862	ENST00000460379.1	TSL:4	c.191C>T	p.Pro64Leu	missense	Exon 4 of 4	ENSP00000417450.1	C9JB70
	ZNF862	ENST00000488265.1	TSL:3	n.-191C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000342 AC: 80 AN: 233756 AF XY: 0.000284

Gnomad AFR exome AF: 0.000142

Gnomad AMR exome AF: 0.0000305

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00149

Gnomad NFE exome AF: 0.000410

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000413 AC: 601 AN: 1454406 Hom.: 1 Cov.: 32 AF XY: 0.000387 AC XY: 280 AN XY: 722816

African (AFR) AF: 0.0000300 AC: 1 AN: 33304

American (AMR) AF: 0.0000231 AC: 1 AN: 43362

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39398

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85230

European-Finnish (FIN) AF: 0.00164 AC: 87 AN: 52952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000444 AC: 492 AN: 1108284

Other (OTH) AF: 0.000299 AC: 18 AN: 60160

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38 AN XY: 74444

African (AFR) AF: 0.0000722 AC: 3 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000441 Hom.: 0

Bravo AF: 0.000283

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000253 AC: 1

ESP6500EA AF: 0.000722 AC: 6

ExAC AF: 0.000331 AC: 40

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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.074
Eigen_PC	Benign	0.031
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.58
MVP		0.067
MPC		0.69
ClinPred		0.30	T
GERP RS		4.4
Varity_R		0.33
gMVP		0.28
Mutation Taster		=97/3	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: rs201261199; hg19: chr7-149545025;