chr19-42387426-C-G

Variant names:

• chr19-42387426-C-G
• rs748701890
• NM_032488.4:c.163G>C

Variant summary

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

The NM_032488.4(CNFN):​c.163G>C​(p.Asp55His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNFN NM_032488.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNFN	NM_032488.4	c.163G>C	p.Asp55His	missense_variant	Exon 3 of 4	ENST00000222032.10	NP_115877.2
CNFN	XM_005259332.4	c.202G>C	p.Asp68His	missense_variant	Exon 4 of 5		XP_005259389.1
CNFN	XM_011527396.3	c.202G>C	p.Asp68His	missense_variant	Exon 4 of 5		XP_011525698.1
CNFN	XM_011527397.3	c.202G>C	p.Asp68His	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.163G>C	p.Asp55His	missense_variant	Exon 3 of 4	1	NM_032488.4	ENSP00000222032.4
CNFN	ENST00000597255.1	c.163G>C	p.Asp55His	missense_variant	Exon 4 of 5	1		ENSP00000469590.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449272 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720144

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.66	.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.090	N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.9	N;.
REVEL	Uncertain	0.48
Sift	Benign	0.38	T;.
Sift4G	Benign	0.17	T;T
Polyphen		1.0	D;D
Vest4		0.60
MutPred		0.56		Loss of stability (P = 0.0885);Loss of stability (P = 0.0885);
MVP		0.46
MPC		0.88
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.46
gMVP		0.73

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

LitVar

Other links and lift over

dbSNP: rs748701890; hg19: chr19-42891578;