NM_182490.3:c.512T>C

Variant names:

• chr19-44234942-T-C
• rs370304805
• NM_182490.3:c.512T>C

Variant summary

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

The NM_182490.3(ZNF227):​c.512T>C​(p.Phe171Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,492 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 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ZNF227 NM_182490.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.85
• 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]

LOC124904726 (HGNC:):

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=0.022544622).

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.512T>C	p.Phe171Ser	missense	Exon 6 of 6	NP_872296.1	Q86WZ6-1
	ZNF227	NM_001289166.2		c.512T>C	p.Phe171Ser	missense	Exon 6 of 6	NP_001276095.1	Q86WZ6-1
	ZNF227	NM_001289173.2		c.428T>C	p.Phe143Ser	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.512T>C	p.Phe171Ser	missense	Exon 6 of 6	ENSP00000321049.6	Q86WZ6-1
	ZNF227	ENST00000621083.4	TSL:2	c.512T>C	p.Phe171Ser	missense	Exon 6 of 6	ENSP00000482749.1	Q86WZ6-1
	ZNF227	ENST00000876872.1		c.512T>C	p.Phe171Ser	missense	Exon 6 of 6	ENSP00000546931.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000520 AC: 13 AN: 249774 AF XY: 0.0000591

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461350 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16 AN XY: 726926

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.000766 AC: 20 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111926

Other (OTH) AF: 0.0000331 AC: 2 AN: 60374

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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: 0.00 AC: 0 AN: 68016

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

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

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	0.061
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.51
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.054	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-1.9
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.032
MVP		0.12
MPC		0.18
ClinPred		0.046	T
GERP RS		-0.85
Varity_R		0.023
gMVP		0.065
Mutation Taster		=99/1	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: rs370304805; hg19: chr19-44739095;