19-42388958-C-A

Variant names:

• chr19-42388958-C-A
• NM_032488.4:c.80G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032488.4(CNFN):​c.80G>T​(p.Gly27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,484 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNFN NM_032488.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNFN	NM_032488.4	c.80G>T	p.Gly27Val	missense_variant	Exon 2 of 4	ENST00000222032.10	NP_115877.2
CNFN	XM_005259332.4	c.119G>T	p.Gly40Val	missense_variant	Exon 3 of 5		XP_005259389.1
CNFN	XM_011527396.3	c.119G>T	p.Gly40Val	missense_variant	Exon 3 of 5		XP_011525698.1
CNFN	XM_011527397.3	c.119G>T	p.Gly40Val	missense_variant	Exon 3 of 5		XP_011525699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNFN	ENST00000222032.10	c.80G>T	p.Gly27Val	missense_variant	Exon 2 of 4	1	NM_032488.4	ENSP00000222032.4
CNFN	ENST00000597255.1	c.80G>T	p.Gly27Val	missense_variant	Exon 3 of 5	1		ENSP00000469590.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461484 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727042

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;D
Eigen	Benign	0.075
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.5	H;H
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.017	D;D
Polyphen		0.76	P;P
Vest4		0.71
MutPred		0.83		Loss of disorder (P = 0.1353);Loss of disorder (P = 0.1353);
MVP		0.54
MPC		1.3
ClinPred		0.93	D
GERP RS		2.5
Varity_R		0.61
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.

Other links and lift over

hg19: chr19-42893110;