chr16-3113479-C-T

Variant names:

• chr16-3113479-C-T
• rs754509014
• NM_001042428.2:c.49C>T

Variant summary

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

The NM_001042428.2(ZNF205):​c.49C>T​(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,094 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 0.0000066 (0 hom., cov: 32)
• Consequence: ZNF205 NM_001042428.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.132
• Publications: 0 publications found

Genes affected

ZNF205 (HGNC:12996): (zinc finger protein 205) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of hydrogen peroxide biosynthetic process; and positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF213-AS1 (HGNC:50505): (ZNF213 antisense RNA 1 (head to head))

ZNF205-AS1 (HGNC:28586): (ZNF205 antisense RNA 1)

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=0.03915307).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042428.2. 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
	ZNF205	NM_001042428.2	MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 2 of 7	NP_001035893.1	O95201
	ZNF205	NM_001278158.2		c.49C>T	p.Pro17Ser	missense	Exon 2 of 7	NP_001265087.1	O95201
	ZNF205	NM_003456.3		c.49C>T	p.Pro17Ser	missense	Exon 2 of 7	NP_003447.2	O95201

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF205	ENST00000219091.9	TSL:5 MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 2 of 7	ENSP00000219091.4	O95201
	ZNF205	ENST00000382192.7	TSL:1	c.49C>T	p.Pro17Ser	missense	Exon 2 of 7	ENSP00000371627.3	O95201
	ZNF205	ENST00000620094.4	TSL:1	c.49C>T	p.Pro17Ser	missense	Exon 2 of 7	ENSP00000480401.1	O95201

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250360 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74282

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

American (AMR) AF: 0.00 AC: 0 AN: 15268

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

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.067
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.1
DANN	Benign	0.78
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.13
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.022
Sift	Benign	0.76	T
Sift4G	Benign	0.35	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.16		Loss of catalytic residue at P17 (P = 0.0016)
MVP		0.26
MPC		0.099
ClinPred		0.047	T
GERP RS		-0.44
Varity_R		0.027
gMVP		0.12

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: rs754509014; hg19: chr16-3163480; COSMIC: COSV104585936; COSMIC: COSV104585936;