16-75169273-C-A

Position:

• chr16-75169273-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153688.4(ZFP1):​c.163C>A​(p.Gln55Lys) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP1 NM_153688.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.883

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]

ZFP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1082367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP1	NM_153688.4	c.163C>A	p.Gln55Lys	missense_variant	4/4	ENST00000570010.6	NP_710155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP1	ENST00000570010.6	c.163C>A	p.Gln55Lys	missense_variant	4/4	2	NM_153688.4	ENSP00000457044.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.163C>A (p.Q55K) alteration is located in exon 4 (coding exon 3) of the ZFP1 gene. This alteration results from a C to A substitution at nucleotide position 163, causing the glutamine (Q) at amino acid position 55 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.062	T;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.028	N
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.28	N;.;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.078
Sift	Benign	0.20	T;D;T
Sift4G	Benign	0.91	T;T;T
Polyphen		0.049	B;.;B
Vest4		0.49
MutPred		0.43		Gain of ubiquitination at Q55 (P = 0.017);.;Gain of ubiquitination at Q55 (P = 0.017);
MVP		0.14
ClinPred		0.25	T
GERP RS		5.0
Varity_R		0.099
gMVP		0.11

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-75203171;