Genetic Variant NM_032488.4:c.163G>T (chr19-42387426-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032488.4(CNFN):c.163G>T(p.Asp55Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000069 in 1,449,272 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: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CNFN
NM_032488.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.14

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNFN	NM_032488.4 link	c.163G>T	p.Asp55Tyr	missense_variant	Exon 3 of 4	ENST00000222032.10	NP_115877.2	Q9BYD5
CNFN	XM_005259332.4 link	c.202G>T	p.Asp68Tyr	missense_variant	Exon 4 of 5		XP_005259389.1
CNFN	XM_011527396.3 link	c.202G>T	p.Asp68Tyr	missense_variant	Exon 4 of 5		XP_011525698.1
CNFN	XM_011527397.3 link	c.202G>T	p.Asp68Tyr	missense_variant	Exon 4 of 5		XP_011525699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNFN	ENST00000222032.10 link	c.163G>T	p.Asp55Tyr	missense_variant	Exon 3 of 4	1	NM_032488.4	ENSP00000222032.4		Q9BYD5
CNFN	ENST00000597255.1 link	c.163G>T	p.Asp55Tyr	missense_variant	Exon 4 of 5	1		ENSP00000469590.1		Q9BYD5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449272

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

.;T

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.80

D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.5

L;L

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.0

D;.

REVEL

Uncertain

0.57

Sift

Uncertain

0.021

D;.

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;D

Vest4

0.71

MutPred

0.56

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.51

MPC

0.90

ClinPred

1.0

GERP RS

4.7

Varity_R

0.57

gMVP

0.78

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over