16-75152957-C-G

Variant names:

• chr16-75152957-C-G
• rs765865676
• NM_153688.4:c.6C>G

Variant summary

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

The NM_153688.4(ZFP1):​c.6C>G​(p.Asn2Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N2N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZFP1 NM_153688.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 0 publications found

Genes affected

ZFP1 (HGNC:23328): (ZFP1 zinc finger protein) This gene belongs to the zinc finger protein family. Some members of this family bind to DNA by zinc-mediated secondary structures called zinc fingers, and are involved in transcriptional regulation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

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=0.21378326).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153688.4. 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
	ZFP1	NM_153688.4	MANE Select	c.6C>G	p.Asn2Lys	missense	Exon 2 of 4	NP_710155.2	Q6P2D0-1
	ZFP1	NM_001318469.2		c.6C>G	p.Asn2Lys	missense	Exon 2 of 4	NP_001305398.1	Q6P2D0-1
	ZFP1	NM_001318475.2		c.6C>G	p.Asn2Lys	missense	Exon 2 of 4	NP_001305404.1	H3BV40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP1	ENST00000570010.6	TSL:2 MANE Select	c.6C>G	p.Asn2Lys	missense	Exon 2 of 4	ENSP00000457044.1	Q6P2D0-1
	ZFP1	ENST00000393430.6	TSL:1	c.6C>G	p.Asn2Lys	missense	Exon 2 of 4	ENSP00000377080.2	Q6P2D0-1
	ZFP1	ENST00000332307.4	TSL:1	c.-85+4314C>G		intron	N/A	ENSP00000333192.4	J3KNQ1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461448 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.53	N
PhyloP100		0.031
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.037
Sift	Benign	0.075	T
Sift4G	Benign	0.72	T
Polyphen		0.043	B
Vest4		0.44
MutPred		0.29		Gain of ubiquitination at N2 (P = 0.0267)
MVP		0.17
ClinPred		0.083	T
GERP RS		0.96
Varity_R		0.046
gMVP		0.11
Mutation Taster		=77/23	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: rs765865676; hg19: chr16-75186855;