rs149222288

Variant names:

• chr16-75169589-A-G
• rs149222288
• NM_153688.4:c.479A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-75169589-A-G
• chr16-75169589-A-C

Variant summary

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

The NM_153688.4(ZFP1):​c.479A>G​(p.Lys160Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000814 in 1,596,418 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 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: ZFP1 NM_153688.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06116274).

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.479A>G	p.Lys160Arg	missense	Exon 4 of 4	NP_710155.2	Q6P2D0-1
	ZFP1	NM_001318469.2		c.479A>G	p.Lys160Arg	missense	Exon 4 of 4	NP_001305398.1	Q6P2D0-1
	ZFP1	NM_001318471.2		c.380A>G	p.Lys127Arg	missense	Exon 5 of 5	NP_001305400.1	J3KNQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP1	ENST00000570010.6	TSL:2 MANE Select	c.479A>G	p.Lys160Arg	missense	Exon 4 of 4	ENSP00000457044.1	Q6P2D0-1
	ZFP1	ENST00000393430.6	TSL:1	c.479A>G	p.Lys160Arg	missense	Exon 4 of 4	ENSP00000377080.2	Q6P2D0-1
	ZFP1	ENST00000332307.4	TSL:1	c.380A>G	p.Lys127Arg	missense	Exon 3 of 3	ENSP00000333192.4	J3KNQ1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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

GnomAD2 exomes AF: 0.0000130 AC: 3 AN: 230008 AF XY: 0.0000240

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000692 AC: 10 AN: 1444190 Hom.: 0 Cov.: 31 AF XY: 0.00000696 AC XY: 5 AN XY: 718178

African (AFR) AF: 0.00 AC: 0 AN: 32022

American (AMR) AF: 0.000257 AC: 10 AN: 38900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 82822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107620

Other (OTH) AF: 0.00 AC: 0 AN: 59470

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

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	0.086
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.029	N
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.8
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.062
Sift	Benign	0.074	T
Sift4G	Benign	0.093	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.32		Loss of ubiquitination at K160 (P = 0.0116)
MVP		0.18
ClinPred		0.10	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.034
gMVP		0.029

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: rs149222288; hg19: chr16-75203487;