chr1-94898074-A-C

Position:

• chr1-94898074-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001839.5(CNN3):​c.658T>G​(p.Leu220Val) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNN3 NM_001839.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

Genes affected

CNN3 (HGNC:2157): (calponin 3) This gene encodes a protein with a markedly acidic C terminus; the basic N-terminus is highly homologous to the N-terminus of a related gene, CNN1. Members of the CNN gene family all contain similar tandemly repeated motifs. This encoded protein is associated with the cytoskeleton but is not involved in contraction. [provided by RefSeq, Jul 2008]

CNN3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1612683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNN3	NM_001839.5	c.658T>G	p.Leu220Val	missense_variant	7/7	ENST00000370206.9	NP_001830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNN3	ENST00000370206.9	c.658T>G	p.Leu220Val	missense_variant	7/7	1	NM_001839.5	ENSP00000359225.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.658T>G (p.L220V) alteration is located in exon 7 (coding exon 7) of the CNN3 gene. This alteration results from a T to G substitution at nucleotide position 658, causing the leucine (L) at amino acid position 220 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.027	.;.;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;.;N;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.18	N;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.051	T;D;D;D
Sift4G	Benign	0.10	T;T;T;.
Polyphen		0.0050	.;.;B;.
Vest4		0.12
MutPred		0.34		.;.;Loss of disorder (P = 0.1896);.;
MVP		0.36
MPC		0.91
ClinPred		0.21	T
GERP RS		4.9
Varity_R		0.066
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-95363630;