rs1277132301

Variant names:

• chr11-57808396-C-G
• rs1277132301
• NM_001085458.2:c.2098C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-57808396-C-G
• chr11-57808396-C-T

Variant summary

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

The NM_001085458.2(CTNND1):​c.2098C>G​(p.Arg700Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 6.9e-7 (0 hom.)
• Consequence: CTNND1 NM_001085458.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 1 publications found

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:):

TMX2-CTNND1 (HGNC:41992): (TMX2-CTNND1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TMX2 (thioredoxin-related transmembrane protein 2) and CTNND1 (catenin, cadherin-associated protein, delta 1) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 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, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNND1	NM_001085458.2	c.2098C>G	p.Arg700Gly	missense_variant	Exon 14 of 21	ENST00000399050.10	NP_001078927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNND1	ENST00000399050.10	c.2098C>G	p.Arg700Gly	missense_variant	Exon 14 of 21	1	NM_001085458.2	ENSP00000382004.5
ENSG00000288534	ENST00000674060.2	n.*2249C>G		non_coding_transcript_exon_variant	Exon 15 of 20			ENSP00000501055.2
ENSG00000288534	ENST00000674060.2	n.*2249C>G		3_prime_UTR_variant	Exon 15 of 20			ENSP00000501055.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246506 AF XY: 0.00000747

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: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453358 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721638

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33224

American (AMR) AF: 0.00 AC: 0 AN: 44274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25850

East Asian (EAS) AF: 0.00 AC: 0 AN: 39526

South Asian (SAS) AF: 0.00 AC: 0 AN: 85708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105830

Other (OTH) AF: 0.00 AC: 0 AN: 59956

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	.;T;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;D;.;.;D;D;D;.;.;.;D;D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.76	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;D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.7	.;.;L;.;.;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;L
PhyloP100		1.5
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	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;N;N;N;N
REVEL	Benign	0.27
Sift	Benign	0.096	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;T;T;T
Sift4G	Benign	0.17	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;T;T;T;T
Polyphen		0.93	P;D;D;.;.;D;.;D;.;.;P;.;.;.;.;.;P;.;.;.;.;D;.;.;D;D;.;.;.;.
Vest4		0.90
MutPred		0.50		.;Loss of MoRF binding (P = 0.0301);Loss of MoRF binding (P = 0.0301);.;.;Loss of MoRF binding (P = 0.0301);.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;Loss of MoRF binding (P = 0.0301);
MVP		0.53
MPC		1.3
ClinPred		0.77	D
GERP RS		3.5
Varity_R		0.48
gMVP		0.64
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: rs1277132301; hg19: chr11-57575868;