16-75169462-G-C

Position:

• chr16-75169462-G-C

Variant summary

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

The NM_153688.4(ZFP1):​c.352G>C​(p.Asp118His) 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. 13/20 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: 0.0530

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

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=0.10336077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP1	NM_153688.4	c.352G>C	p.Asp118His	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.352G>C	p.Asp118His	missense_variant	4/4	2	NM_153688.4	ENSP00000457044	P1

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

Jun 05, 2023

The c.352G>C (p.D118H) alteration is located in exon 4 (coding exon 3) of the ZFP1 gene. This alteration results from a G to C substitution at nucleotide position 352, causing the aspartic acid (D) at amino acid position 118 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.051	N
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.085	N;.;N
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N;D;N
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.013	D;T;D
Polyphen		0.0030	B;.;B
Vest4		0.47
MutPred		0.23		Loss of ubiquitination at K114 (P = 0.0464);.;Loss of ubiquitination at K114 (P = 0.0464);
MVP		0.19
ClinPred		0.59	D
GERP RS		4.5
Varity_R		0.19
gMVP		0.41

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-75203360;