rs16982871

Variant names:

• chr22-19978040-C-G
• rs16982871
• NM_001670.3:c.1616G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-19978040-C-G
• chr22-19978040-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001670.3(ARVCF):​c.1616G>C​(p.Arg539Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R539Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARVCF NM_001670.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARVCF	NM_001670.3	c.1616G>C	p.Arg539Pro	missense_variant	Exon 8 of 20	ENST00000263207.8	NP_001661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARVCF	ENST00000263207.8	c.1616G>C	p.Arg539Pro	missense_variant	Exon 8 of 20	1	NM_001670.3	ENSP00000263207.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Pathogenic	2.9	M;.;.;.
PhyloP100		2.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.3	D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.73
MutPred		0.42		Loss of MoRF binding (P = 0.0306);.;.;Loss of MoRF binding (P = 0.0306);
MVP		0.92
MPC		0.62
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.89
gMVP		0.88
Mutation Taster		=51/49	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: rs16982871; hg19: chr22-19965563;