rs758952416

Variant names:

• chr19-44235284-G-A
• rs758952416
• NM_182490.3:c.854G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-44235284-G-A
• chr19-44235284-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_182490.3(ZNF227):​c.854G>A​(p.Arg285Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,948 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: ZNF227 NM_182490.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268
• Publications: 0 publications found

Genes affected

ZNF227 (HGNC:13020): (zinc finger protein 227) Predicted to enable DNA-binding transcription activator 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 act upstream of or within negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF235 (HGNC:12866): (zinc finger protein 235) This gene product belongs to the zinc finger protein superfamily, members of which are regulatory proteins characterized by nucleic acid-binding zinc finger domains. The encoded protein is a member of the Kruppel family of zinc finger proteins, and contains Kruppel-associated box (KRAB) A and B domains and 15 tandemly arrayed C2H2-type zinc fingers. It is an ortholog of the mouse Zfp93 protein. This gene is located in a cluster of zinc finger genes on 19q13.2. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018310755).
• BP6: Variant 19-44235284-G-A is Benign according to our data. Variant chr19-44235284-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3820046.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182490.3. 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
	ZNF227	NM_182490.3	MANE Select	c.854G>A	p.Arg285Gln	missense	Exon 6 of 6	NP_872296.1	Q86WZ6-1
	ZNF227	NM_001289166.2		c.854G>A	p.Arg285Gln	missense	Exon 6 of 6	NP_001276095.1	Q86WZ6-1
	ZNF227	NM_001289173.2		c.770G>A	p.Arg257Gln	missense	Exon 5 of 5	NP_001276102.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF227	ENST00000313040.12	TSL:1 MANE Select	c.854G>A	p.Arg285Gln	missense	Exon 6 of 6	ENSP00000321049.6	Q86WZ6-1
	ZNF227	ENST00000621083.4	TSL:2	c.854G>A	p.Arg285Gln	missense	Exon 6 of 6	ENSP00000482749.1	Q86WZ6-1
	ZNF227	ENST00000876872.1		c.854G>A	p.Arg285Gln	missense	Exon 6 of 6	ENSP00000546931.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.000288

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: 0.000478

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250952 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 35 AN: 1461858 Hom.: 0 Cov.: 34 AF XY: 0.0000234 AC XY: 17 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000224 AC: 10 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152090 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.000197 AC: 3 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.059
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.8
DANN	Benign	0.42
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.071	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.10	N
PhyloP100		-0.27
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.83	N
REVEL	Benign	0.014
Sift	Benign	1.0	T
Sift4G	Benign	0.62	T
Polyphen		0.0010	B
Vest4		0.044
MutPred		0.27		Loss of catalytic residue at R285 (P = 0.0169)
MVP		0.10
MPC		0.11
ClinPred		0.0098	T
GERP RS		1.8
Varity_R		0.018
gMVP		0.031
Mutation Taster		=98/2	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: rs758952416; hg19: chr19-44739437; COSMIC: COSV106096806; COSMIC: COSV106096806;