Variant 19-42389007-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032488.4(CNFN):c.31T>G(p.Cys11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CNFN
NM_032488.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.442

Variant links:

Genes affected

CNFN (HGNC:30183): (cornifelin) Predicted to be involved in keratinization. Located in cornified envelope. [provided by Alliance of Genome Resources, Apr 2022]

CNFN links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054520726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNFN	NM_032488.4 linkuse as main transcript	c.31T>G	p.Cys11Gly	missense_variant	2/4	ENST00000222032.10	NP_115877.2	Q9BYD5
CNFN	XM_005259332.4 linkuse as main transcript	c.70T>G	p.Cys24Gly	missense_variant	3/5		XP_005259389.1
CNFN	XM_011527396.3 linkuse as main transcript	c.70T>G	p.Cys24Gly	missense_variant	3/5		XP_011525698.1
CNFN	XM_011527397.3 linkuse as main transcript	c.70T>G	p.Cys24Gly	missense_variant	3/5		XP_011525699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNFN	ENST00000222032.10 linkuse as main transcript	c.31T>G	p.Cys11Gly	missense_variant	2/4	1	NM_032488.4	ENSP00000222032.4		Q9BYD5
CNFN	ENST00000597255.1 linkuse as main transcript	c.31T>G	p.Cys11Gly	missense_variant	3/5	1		ENSP00000469590.1		Q9BYD5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250264

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461486

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2024

The c.31T>G (p.C11G) alteration is located in exon 2 (coding exon 1) of the CNFN gene. This alteration results from a T to G substitution at nucleotide position 31, causing the cysteine (C) at amino acid position 11 to be replaced by a glycine (G). 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

0.052

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.017

T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.48

.;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.63

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

1.3

N;.

REVEL

Benign

0.044

Sift

Benign

0.33

T;.

Sift4G

Benign

0.33

T;T

Polyphen

0.0

B;B

Vest4

0.30

MutPred

0.28

Loss of stability (P = 0.0481);Loss of stability (P = 0.0481);

MVP

0.085

MPC

0.46

ClinPred

0.027

GERP RS

1.1

Varity_R

0.085

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over