NM_153688.4:c.144A>C

Variant names:

• chr16-75169254-A-C
• rs376091706
• NM_153688.4:c.144A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 17/24 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20878407).

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.144A>C	p.Glu48Asp	missense splice_region	Exon 4 of 4	NP_710155.2	Q6P2D0-1
	ZFP1	NM_001318469.2		c.144A>C	p.Glu48Asp	missense splice_region	Exon 4 of 4	NP_001305398.1	Q6P2D0-1
	ZFP1	NM_001318471.2		c.45A>C	p.Glu15Asp	missense splice_region	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.144A>C	p.Glu48Asp	missense splice_region	Exon 4 of 4	ENSP00000457044.1	Q6P2D0-1
	ZFP1	ENST00000393430.6	TSL:1	c.144A>C	p.Glu48Asp	missense splice_region	Exon 4 of 4	ENSP00000377080.2	Q6P2D0-1
	ZFP1	ENST00000332307.4	TSL:1	c.45A>C	p.Glu15Asp	missense splice_region	Exon 3 of 3	ENSP00000333192.4	J3KNQ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.043	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
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.84	L
PhyloP100		0.74
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.062
Sift	Benign	0.17	T
Sift4G	Benign	0.21	T
Polyphen		0.72	P
Vest4		0.50
MutPred		0.39		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

Other links and lift over

dbSNP: rs376091706; hg19: chr16-75203152;