rs962340710

Variant names:

• chr16-3115553-T-C
• rs962340710
• NM_001042428.2:c.256T>C

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.256T>C​(p.Phe86Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,592,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF205 NM_001042428.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26
• 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=0.05905646).

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.256T>C	p.Phe86Leu	missense	Exon 3 of 7	NP_001035893.1	O95201
	ZNF205	NM_001278158.2		c.256T>C	p.Phe86Leu	missense	Exon 3 of 7	NP_001265087.1	O95201
	ZNF205	NM_003456.3		c.256T>C	p.Phe86Leu	missense	Exon 3 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.256T>C	p.Phe86Leu	missense	Exon 3 of 7	ENSP00000219091.4	O95201
	ZNF205	ENST00000382192.7	TSL:1	c.256T>C	p.Phe86Leu	missense	Exon 3 of 7	ENSP00000371627.3	O95201
	ZNF205	ENST00000620094.4	TSL:1	c.256T>C	p.Phe86Leu	missense	Exon 3 of 7	ENSP00000480401.1	O95201

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440316 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 716268

African (AFR) AF: 0.0000312 AC: 1 AN: 32020

American (AMR) AF: 0.00 AC: 0 AN: 38464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 38948

South Asian (SAS) AF: 0.00 AC: 0 AN: 82708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104760

Other (OTH) AF: 0.00 AC: 0 AN: 59438

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152186 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74354

African (AFR) AF: 0.0000724 AC: 3 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	Uncertain	0.52
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.64
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.85	L
PhyloP100		-1.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.041
Sift	Benign	0.71	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.30		Gain of disorder (P = 0.0611)
MVP		0.42
MPC		0.12
ClinPred		0.046	T
GERP RS		0.72
PromoterAI		-0.046	Neutral
Varity_R		0.042
gMVP		0.096

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: rs962340710; hg19: chr16-3165554;