chr16-3118962-C-T

Variant names:

• chr16-3118962-C-T
• rs189840930
• NM_001042428.2:c.542C>T

Variant summary

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

The NM_001042428.2(ZNF205):​c.542C>T​(p.Ser181Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,636 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 0.000098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ZNF205 NM_001042428.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.126
• 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))

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02909097).

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.542C>T	p.Ser181Leu	missense	Exon 6 of 7	NP_001035893.1	O95201
	ZNF205	NM_001278158.2		c.542C>T	p.Ser181Leu	missense	Exon 6 of 7	NP_001265087.1	O95201
	ZNF205	NM_003456.3		c.542C>T	p.Ser181Leu	missense	Exon 6 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.542C>T	p.Ser181Leu	missense	Exon 6 of 7	ENSP00000219091.4	O95201
	ZNF205	ENST00000382192.7	TSL:1	c.542C>T	p.Ser181Leu	missense	Exon 6 of 7	ENSP00000371627.3	O95201
	ZNF205	ENST00000620094.4	TSL:1	c.542C>T	p.Ser181Leu	missense	Exon 6 of 7	ENSP00000480401.1	O95201

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152182 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.0000519 AC: 13 AN: 250352 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461334 Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20 AN XY: 726980

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000730 AC: 29 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52934

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

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152302 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74484

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.000719 AC: 11 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000982

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	0.13
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.66	N
PhyloP100		0.13
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.010
Sift	Benign	0.29	T
Sift4G	Benign	0.29	T
Polyphen		0.013	B
Vest4		0.22
MVP		0.36
MPC		0.091
ClinPred		0.012	T
GERP RS		2.8
Varity_R		0.064
gMVP		0.099
Mutation Taster		=83/17	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: rs189840930; hg19: chr16-3168963; COSMIC: COSV54620416; COSMIC: COSV54620416;