16-3113462-C-G

Variant names:

• chr16-3113462-C-G
• rs137889671
• NM_001042428.2:c.32C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042428.2(ZNF205):​c.32C>G​(p.Thr11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,280 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF205 NM_001042428.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.768
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09491101).

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.32C>G	p.Thr11Ser	missense	Exon 2 of 7	NP_001035893.1	O95201
	ZNF205	NM_001278158.2		c.32C>G	p.Thr11Ser	missense	Exon 2 of 7	NP_001265087.1	O95201
	ZNF205	NM_003456.3		c.32C>G	p.Thr11Ser	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.32C>G	p.Thr11Ser	missense	Exon 2 of 7	ENSP00000219091.4	O95201
	ZNF205	ENST00000382192.7	TSL:1	c.32C>G	p.Thr11Ser	missense	Exon 2 of 7	ENSP00000371627.3	O95201
	ZNF205	ENST00000620094.4	TSL:1	c.32C>G	p.Thr11Ser	missense	Exon 2 of 7	ENSP00000480401.1	O95201

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250694 AF XY: 0.00000738

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461280 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726960

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111748

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	0.092
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.77
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.067
Sift	Benign	0.058	T
Sift4G	Benign	0.12	T
Polyphen		0.043	B
Vest4		0.16
MutPred		0.087		Loss of glycosylation at T11 (P = 0.0705)
MVP		0.66
MPC		0.10
ClinPred		0.053	T
GERP RS		3.0
Varity_R		0.099
gMVP		0.074
Mutation Taster		=96/4	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: rs137889671; hg19: chr16-3163463;