Variant chr19-42387449-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032488.4(CNFN):c.140G>T(p.Cys47Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,593,920 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CNFN
NM_032488.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNFN	NM_032488.4 linkuse as main transcript	c.140G>T	p.Cys47Phe	missense_variant	3/4	ENST00000222032.10	NP_115877.2	Q9BYD5
CNFN	XM_005259332.4 linkuse as main transcript	c.179G>T	p.Cys60Phe	missense_variant	4/5		XP_005259389.1
CNFN	XM_011527396.3 linkuse as main transcript	c.179G>T	p.Cys60Phe	missense_variant	4/5		XP_011525698.1
CNFN	XM_011527397.3 linkuse as main transcript	c.179G>T	p.Cys60Phe	missense_variant	4/5		XP_011525699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNFN	ENST00000222032.10 linkuse as main transcript	c.140G>T	p.Cys47Phe	missense_variant	3/4	1	NM_032488.4	ENSP00000222032.4		Q9BYD5
CNFN	ENST00000597255.1 linkuse as main transcript	c.140G>T	p.Cys47Phe	missense_variant	4/5	1		ENSP00000469590.1		Q9BYD5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000143

AC:

AN:

209074

Hom.:

AF XY:

0.00

AC XY:

AN XY:

114612

show subpopulations

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:

0.0000367

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000219

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1441774

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

715878

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000181

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000833

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

Aug 19, 2024

The c.140G>T (p.C47F) alteration is located in exon 3 (coding exon 2) of the CNFN gene. This alteration results from a G to T substitution at nucleotide position 140, causing the cysteine (C) at amino acid position 47 to be replaced by a phenylalanine (F). 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

0.20

BayesDel_addAF

Benign

0.0051

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-7.4

D;.

REVEL

Uncertain

0.36

Sift

Benign

0.060

T;.

Sift4G

Uncertain

0.012

D;D

Polyphen

0.26

B;B

Vest4

0.70

MutPred

0.69

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.38

MPC

1.3

ClinPred

0.88

GERP RS

3.7

Varity_R

0.55

gMVP

0.69

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