chr17-57974721-T-G

Variant names:

• chr17-57974721-T-G
• rs759084866
• NM_007146.3:c.1318A>C

Variant summary

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

The NM_007146.3(VEZF1):​c.1318A>C​(p.Met440Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VEZF1 NM_007146.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61

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]

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=0.12965816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEZF1	NM_007146.3	c.1318A>C	p.Met440Leu	missense_variant	Exon 6 of 6	ENST00000581208.2	NP_009077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEZF1	ENST00000581208.2	c.1318A>C	p.Met440Leu	missense_variant	Exon 6 of 6	1	NM_007146.3	ENSP00000462337.1
VEZF1	ENST00000258963.7	c.772A>C	p.Met258Leu	missense_variant	Exon 5 of 5	1		ENSP00000258963.3
VEZF1	ENST00000584396.5	c.1291A>C	p.Met431Leu	missense_variant	Exon 6 of 6	5		ENSP00000464687.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251468 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.0089	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Uncertain	0.60	T
Sift4G	Benign	0.41	T;T
Polyphen		0.030	.;B
Vest4		0.39
MutPred		0.19		.;Gain of sheet (P = 0.1208);
MVP		0.22
MPC		0.74
ClinPred		0.33	T
GERP RS		4.9
Varity_R		0.41
gMVP		0.36

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

Other links and lift over

dbSNP: rs759084866; hg19: chr17-56052082;