NM_007146.3:c.1047A>G

Variant names:

• chr17-57979243-T-C
• rs138088904
• NM_007146.3:c.1047A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_007146.3(VEZF1):​c.1047A>G​(p.Gln349Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00088 in 1,596,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00089 (1 hom.)
• Consequence: VEZF1 NM_007146.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.805
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• cardiomyopathy, dilated, 100

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-57979243-T-C is Benign according to our data. Variant chr17-57979243-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 728195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.805 with no splicing effect.
• BS2: High AC in GnomAd4 at 118 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007146.3. 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
	VEZF1	NM_007146.3	MANE Select	c.1047A>G	p.Gln349Gln	synonymous	Exon 5 of 6	NP_009077.2	Q14119
	VEZF1	NM_001330393.2		c.1020A>G	p.Gln340Gln	synonymous	Exon 6 of 7	NP_001317322.1	J3QSH4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEZF1	ENST00000581208.2	TSL:1 MANE Select	c.1047A>G	p.Gln349Gln	synonymous	Exon 5 of 6	ENSP00000462337.1	Q14119
	VEZF1	ENST00000258963.7	TSL:1	c.501A>G	p.Gln167Gln	synonymous	Exon 4 of 5	ENSP00000258963.3	J9JIC7
	VEZF1	ENST00000905172.1		c.1188A>G	p.Gln396Gln	synonymous	Exon 6 of 7	ENSP00000575231.1

Frequencies

GnomAD3 genomes AF: 0.000783 AC: 118 AN: 150648 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000687

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.000288

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00117

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.000891 AC: 1288 AN: 1446204 Hom.: 1 Cov.: 32 AF XY: 0.000955 AC XY: 687 AN XY: 719454

African (AFR) AF: 0.000729 AC: 24 AN: 32926

American (AMR) AF: 0.000699 AC: 31 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.00101 AC: 26 AN: 25808

East Asian (EAS) AF: 0.000178 AC: 7 AN: 39308

South Asian (SAS) AF: 0.000248 AC: 21 AN: 84796

European-Finnish (FIN) AF: 0.000152 AC: 8 AN: 52616

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5636

European-Non Finnish (NFE) AF: 0.00102 AC: 1122 AN: 1101132

Other (OTH) AF: 0.000788 AC: 47 AN: 59662

GnomAD4 genome AF: 0.000783 AC: 118 AN: 150760 Hom.: 0 Cov.: 29 AF XY: 0.000611 AC XY: 45 AN XY: 73668

African (AFR) AF: 0.000685 AC: 28 AN: 40900

American (AMR) AF: 0.000264 AC: 4 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.000580 AC: 2 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000210 AC: 1 AN: 4752

European-Finnish (FIN) AF: 0.000288 AC: 3 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00117 AC: 79 AN: 67638

Other (OTH) AF: 0.000479 AC: 1 AN: 2086

Alfa AF: 0.00196 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.15
DANN	Benign	0.26
PhyloP100		-0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138088904; hg19: chr17-56056604; COSMIC: COSV51967854; COSMIC: COSV51967854;