Genetic Variant NM_007146.3:c.1041_1042delGC (chr17-57979247-TGC-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PVS1_StrongBP6BS1BS2

The NM_007146.3(VEZF1):c.1041_1042delGC(p.Gln348AlafsTer27) variant causes a frameshift change. The variant allele was found at a frequency of 0.00377 in 1,574,920 control chromosomes in the GnomAD database, including 69 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0073 ( 13 hom., cov: 31)

Exomes 𝑓: 0.0034 ( 56 hom. )

Consequence

VEZF1
NM_007146.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

VEZF1 (HGNC:12949): (vascular endothelial zinc finger 1) Transcriptional regulatory proteins containing tandemly repeated zinc finger domains are thought to be involved in both normal and abnormal cellular proliferation and differentiation. ZNF161 is a C2H2-type zinc finger protein (Koyano-Nakagawa et al., 1994 [PubMed 8035792]). See MIM 603971 for general information on zinc finger proteins.[supplied by OMIM, Sep 2008]

VEZF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.335 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 17-57979247-TGC-T is Benign according to our data. Variant chr17-57979247-TGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056939.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00734 (1040/141600) while in subpopulation SAS AF= 0.0282 (132/4676). AF 95% confidence interval is 0.0243. There are 13 homozygotes in gnomad4. There are 549 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1040 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEZF1	NM_007146.3 link	c.1041_1042delGC	p.Gln348AlafsTer27	frameshift_variant	Exon 5 of 6	ENST00000581208.2	NP_009077.2	Q14119

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VEZF1	ENST00000581208.2 link	c.1041_1042delGC	p.Gln348AlafsTer27	frameshift_variant	Exon 5 of 6	1	NM_007146.3	ENSP00000462337.1	Q14119
VEZF1	ENST00000258963.7 link	c.495_496delGC	p.Gln166fs	frameshift_variant	Exon 4 of 5	1		ENSP00000258963.3	J9JIC7
VEZF1	ENST00000584396.5 link	c.1014_1015delGC	p.Gln339AlafsTer27	frameshift_variant	Exon 5 of 6	5		ENSP00000464687.1	J3QSH4

Frequencies

GnomAD3 genomes

AF:

0.00727

AC:

1028

AN:

141492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00474

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0000973

Gnomad MID

AF:

0.0130

Gnomad NFE

AF:

0.00205

Gnomad OTH

AF:

0.00502

GnomAD3 exomes

AF:

0.0000987

AC:

AN:

233112

Hom.:

AF XY:

0.0000944

AC XY:

AN XY:

127112

show subpopulations

Gnomad AFR exome

AF:

0.000306

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.0000989

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00342

AC:

4897

AN:

1433320

Hom.:

AF XY:

0.00398

AC XY:

2841

AN XY:

713132

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0251

Gnomad4 FIN exome

AF:

0.000248

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.00492

GnomAD4 genome

AF:

0.00734

AC:

1040

AN:

141600

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

549

AN XY:

69384

show subpopulations

Gnomad4 AFR

AF:

0.0199

Gnomad4 AMR

AF:

0.00473

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0282

Gnomad4 FIN

AF:

0.0000973

Gnomad4 NFE

AF:

0.00205

Gnomad4 OTH

AF:

0.00595

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

VEZF1-related disorder

Benign:1

Apr 11, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over