16-3118987-T-G

Variant names:

• chr16-3118987-T-G
• rs529019314
• NM_001042428.2:c.567T>G

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.567T>G​(p.Asp189Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF205 NM_001042428.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043067336).

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.567T>G	p.Asp189Glu	missense	Exon 6 of 7	NP_001035893.1	O95201
	ZNF205	NM_001278158.2		c.567T>G	p.Asp189Glu	missense	Exon 6 of 7	NP_001265087.1	O95201
	ZNF205	NM_003456.3		c.567T>G	p.Asp189Glu	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.567T>G	p.Asp189Glu	missense	Exon 6 of 7	ENSP00000219091.4	O95201
	ZNF205	ENST00000382192.7	TSL:1	c.567T>G	p.Asp189Glu	missense	Exon 6 of 7	ENSP00000371627.3	O95201
	ZNF205	ENST00000620094.4	TSL:1	c.567T>G	p.Asp189Glu	missense	Exon 6 of 7	ENSP00000480401.1	O95201

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.099
DANN	Benign	0.44
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.74	N
PhyloP100		-1.0
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.021
Sift	Benign	0.91	T
Sift4G	Benign	0.71	T
Polyphen		0.0020	B
Vest4		0.098
MutPred		0.23		Loss of helix (P = 0.0558)
MVP		0.20
MPC		0.092
ClinPred		0.051	T
GERP RS		-4.4
Varity_R		0.039
gMVP		0.064

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs529019314; hg19: chr16-3168988;