NM_001670.3:c.2829G>T

Variant names:

• chr22-19971288-C-A
• rs35219372
• NM_001670.3:c.2829G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001670.3(ARVCF):​c.2829G>T​(p.Ala943Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000385 in 1,556,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ARVCF NM_001670.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 4 publications found

Genes affected

ARVCF (HGNC:728): (ARVCF delta catenin family member) Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (ARVCF) is a member of the catenin family. This family plays an important role in the formation of adherens junction complexes, which are thought to facilitate communication between the inside and outside environments of a cell. The ARVCF gene was isolated in the search for the genetic defect responsible for the autosomal dominant Velo-Cardio-Facial syndrome (VCFS), a relatively common human disorder with phenotypic features including cleft palate, conotruncal heart defects and facial dysmorphology. The ARVCF gene encodes a protein containing two motifs, a coiled coil domain in the N-terminus and a 10 armadillo repeat sequence in the midregion. Since these sequences can facilitate protein-protein interactions ARVCF is thought to function in a protein complex. In addition, ARVCF contains a predicted nuclear-targeting sequence suggesting that it may have a function as a nuclear protein. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001670.3. 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
	ARVCF	NM_001670.3	MANE Select	c.2829G>T	p.Ala943Ala	synonymous	Exon 19 of 20	NP_001661.1
	ARVCF	NM_001438684.1		c.2811G>T	p.Ala937Ala	synonymous	Exon 18 of 18	NP_001425613.1
	ARVCF	NM_001438685.1		c.2796G>T	p.Ala932Ala	synonymous	Exon 18 of 19	NP_001425614.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARVCF	ENST00000263207.8	TSL:1 MANE Select	c.2829G>T	p.Ala943Ala	synonymous	Exon 19 of 20	ENSP00000263207.3
	ARVCF	ENST00000406259.1	TSL:5	c.2811G>T	p.Ala937Ala	synonymous	Exon 16 of 16	ENSP00000385444.1
	ARVCF	ENST00000852538.1		c.2796G>T	p.Ala932Ala	synonymous	Exon 18 of 19	ENSP00000522597.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000613 AC: 1 AN: 163106 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000156

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000285 AC: 4 AN: 1404688 Hom.: 0 Cov.: 35 AF XY: 0.00000288 AC XY: 2 AN XY: 693342

African (AFR) AF: 0.00 AC: 0 AN: 32162

American (AMR) AF: 0.00 AC: 0 AN: 36660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25214

East Asian (EAS) AF: 0.00 AC: 0 AN: 36528

South Asian (SAS) AF: 0.00 AC: 0 AN: 79842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1081738

Other (OTH) AF: 0.00 AC: 0 AN: 58164

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 51

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	0.21
DANN	Benign	0.92
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35219372; hg19: chr22-19958811;