11-57796686-A-G

Position:

• chr11-57796686-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001085458.2(CTNND1):​c.650A>G​(p.Tyr217Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,996 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: CTNND1 NM_001085458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92

Genes affected

CTNND1 (HGNC:2515): (catenin delta 1) This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Read-through transcription also exists between this gene and the neighboring upstream thioredoxin-related transmembrane protein 2 (TMX2) gene. [provided by RefSeq, Dec 2010]

ENSG00000288534 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24645746).
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000028 (41/1461706) while in subpopulation SAS AF= 0.000359 (31/86256). AF 95% confidence interval is 0.00026. There are 0 homozygotes in gnomad4_exome. There are 26 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNND1	NM_001085458.2	c.650A>G	p.Tyr217Cys	missense_variant	6/21	ENST00000399050.10	NP_001078927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNND1	ENST00000399050.10	c.650A>G	p.Tyr217Cys	missense_variant	6/21	1	NM_001085458.2	ENSP00000382004.5
ENSG00000288534	ENST00000674060.1	n.*801A>G		non_coding_transcript_exon_variant	7/20			ENSP00000501055.2
ENSG00000288534	ENST00000674060.1	n.*801A>G		3_prime_UTR_variant	7/20			ENSP00000501055.2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152172 Hom.: 0 Cov.: 31

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: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000281 AC: 7 AN: 249346 Hom.: 0 AF XY: 0.0000296 AC XY: 4 AN XY: 135254

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 SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461706 Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 26 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152290 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ExAC AF: 0.0000577 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	.;T;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	.;D;D;.;.;D;D;D;.;.;.;D;.;.;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.066	T
MutationAssessor	Uncertain	2.2	M;.;M;.;.;M;M;M;.;.;M;.;.;.;.;M;.;.;.;.;.;.;.;.;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.3	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.018	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.060	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;D
Polyphen		1.0	D;D;D;.;.;D;.;D;.;.;D;.;.;.;.;D;.;D;.;D;.;.;.;.;.;.
Vest4		0.91
MutPred		0.15		Loss of phosphorylation at Y217 (P = 0.0174);Loss of phosphorylation at Y217 (P = 0.0174);Loss of phosphorylation at Y217 (P = 0.0174);.;.;Loss of phosphorylation at Y217 (P = 0.0174);Loss of phosphorylation at Y217 (P = 0.0174);Loss of phosphorylation at Y217 (P = 0.0174);.;.;Loss of phosphorylation at Y217 (P = 0.0174);.;.;.;.;Loss of phosphorylation at Y217 (P = 0.0174);.;.;.;.;.;.;.;.;Loss of phosphorylation at Y217 (P = 0.0174);.;
MVP		0.85
MPC		1.2
ClinPred		0.36	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.86

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: rs11570194; hg19: chr11-57564158;