16-75169254-A-C

Position:

• chr16-75169254-A-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.144A>C​(p.Glu48Asp) variant causes a missense, splice region 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. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP1 NM_153688.4 missense, splice_region
• Scores: Splicing: ADA: 0.00002494
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.741

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=0.20878407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP1	NM_153688.4	c.144A>C	p.Glu48Asp	missense_variant, splice_region_variant	4/4	ENST00000570010.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP1	ENST00000570010.6	c.144A>C	p.Glu48Asp	missense_variant, splice_region_variant	4/4	2	NM_153688.4	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

Sep 06, 2023

The c.144A>C (p.E48D) alteration is located in exon 4 (coding exon 3) of the ZFP1 gene. This alteration results from a A to C substitution at nucleotide position 144, causing the glutamic acid (E) at amino acid position 48 to be replaced by an aspartic acid (D). 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	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.043	T;.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.30	N
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.84	L;.;L
MutationTaster	Benign	0.93	N;N;N;N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.70	N;N;N
REVEL	Benign	0.062
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.72	P;.;P
Vest4		0.50
MutPred		0.39		Loss of catalytic residue at W50 (P = 0.0768);.;Loss of catalytic residue at W50 (P = 0.0768);
MVP		0.19
ClinPred		0.63	D
GERP RS		1.6
Varity_R		0.041
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: chr16-75203152;