chr19-42387444-C-G

Variant names:

• chr19-42387444-C-G
• NM_032488.4:c.145G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032488.4(CNFN):​c.145G>C​(p.Ala49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,460 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

Genes affected

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

ACMG classification

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, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNFN	NM_032488.4	c.145G>C	p.Ala49Pro	missense_variant	Exon 3 of 4	ENST00000222032.10	NP_115877.2
CNFN	XM_005259332.4	c.184G>C	p.Ala62Pro	missense_variant	Exon 4 of 5		XP_005259389.1
CNFN	XM_011527396.3	c.184G>C	p.Ala62Pro	missense_variant	Exon 4 of 5		XP_011525698.1
CNFN	XM_011527397.3	c.184G>C	p.Ala62Pro	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	c.145G>C	p.Ala49Pro	missense_variant	Exon 3 of 4	1	NM_032488.4	ENSP00000222032.4
CNFN	ENST00000597255.1	c.145G>C	p.Ala49Pro	missense_variant	Exon 4 of 5	1		ENSP00000469590.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444460 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 717412

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000234

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.077	T;T
Eigen	Benign	0.069
Eigen_PC	Benign	-0.034
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.71	.;T
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N;.
REVEL	Uncertain	0.36
Sift	Benign	0.16	T;.
Sift4G	Benign	0.13	T;T
Polyphen		0.98	D;D
Vest4		0.88
MutPred		0.66		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.34
MPC		0.96
ClinPred		0.85	D
GERP RS		2.6
Varity_R		0.51
gMVP		0.88

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-42891596;