16-75169310-C-T

Variant names:

• chr16-75169310-C-T
• rs949971145
• NM_153688.4:c.200C>T

Variant summary

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

The NM_001318475.2(ZFP1):​c.217C>T​(p.Arg73*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ZFP1 NM_001318475.2 stop_gained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.567
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318475.2. 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
	ZFP1	NM_153688.4	MANE Select	c.200C>T	p.Ala67Val	missense	Exon 4 of 4	NP_710155.2	Q6P2D0-1
	ZFP1	NM_001318475.2		c.217C>T	p.Arg73*	stop_gained	Exon 4 of 4	NP_001305404.1	H3BV40
	ZFP1	NM_001318476.2		c.217C>T	p.Arg73*	stop_gained	Exon 4 of 4	NP_001305405.1	H3BV40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP1	ENST00000570010.6	TSL:2 MANE Select	c.200C>T	p.Ala67Val	missense	Exon 4 of 4	ENSP00000457044.1	Q6P2D0-1
	ZFP1	ENST00000393430.6	TSL:1	c.200C>T	p.Ala67Val	missense	Exon 4 of 4	ENSP00000377080.2	Q6P2D0-1
	ZFP1	ENST00000332307.4	TSL:1	c.101C>T	p.Ala34Val	missense	Exon 3 of 3	ENSP00000333192.4	J3KNQ1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151968 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461738 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727170

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44668

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111964

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151968 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74218

African (AFR) AF: 0.0000242 AC: 1 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

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	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.080	N
PhyloP100		-0.57
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.015
Sift	Benign	0.62	T
Sift4G	Benign	0.61	T
Polyphen		0.0020	B
Vest4		0.20
MutPred		0.29		Loss of disorder (P = 0.0828)
MVP		0.11
ClinPred		0.064	T
GERP RS		0.66
Varity_R		0.015
gMVP		0.098
Mutation Taster		=175/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs949971145; hg19: chr16-75203208;