rs995729163

Variant names:

• chr1-151518944-C-T
• rs995729163
• NM_020770.3:c.425C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020770.3(CGN):​c.425C>T​(p.Ala142Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: CGN NM_020770.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.165
• Publications: 0 publications found

Genes affected

CGN (HGNC:17429): (cingulin) Enables cadherin binding activity. Predicted to act upstream of or within bicellular tight junction assembly; epithelial cell morphogenesis; and microtubule cytoskeleton organization. Located in bicellular tight junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056252122).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020770.3. 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
	CGN	NM_020770.3	MANE Select	c.425C>T	p.Ala142Val	missense	Exon 2 of 21	NP_065821.1	Q9P2M7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGN	ENST00000271636.12	TSL:1 MANE Select	c.425C>T	p.Ala142Val	missense	Exon 2 of 21	ENSP00000271636.7	Q9P2M7-1
	CGN	ENST00000502442.1	TSL:1	c.425C>T	p.Ala142Val	missense	Exon 2 of 2	ENSP00000422299.1	A2A3M4
	CGN	ENST00000505188.5	TSL:1	c.425C>T	p.Ala142Val	missense	Exon 2 of 2	ENSP00000425532.1	A2A3M4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 10 AN: 251294 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000581 AC: 85 AN: 1461860 Hom.: 0 Cov.: 32 AF XY: 0.0000523 AC XY: 38 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000665 AC: 74 AN: 1111990

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000189

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.17
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.062
Sift	Benign	0.094	T
Sift4G	Benign	0.39	T
Vest4		0.12
MVP		0.37
MPC		0.16
ClinPred		0.057	T
GERP RS		2.2
PromoterAI		0.027	Neutral
gMVP		0.13
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs995729163; hg19: chr1-151491420;