19-42387444-C-T

Variant names:

• chr19-42387444-C-T
• rs1473289137
• NM_032488.4:c.145G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032488.4(CNFN):​c.145G>A​(p.Ala49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33214962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNFN	NM_032488.4	c.145G>A	p.Ala49Thr	missense_variant	Exon 3 of 4	ENST00000222032.10	NP_115877.2
CNFN	XM_005259332.4	c.184G>A	p.Ala62Thr	missense_variant	Exon 4 of 5		XP_005259389.1
CNFN	XM_011527396.3	c.184G>A	p.Ala62Thr	missense_variant	Exon 4 of 5		XP_011525698.1
CNFN	XM_011527397.3	c.184G>A	p.Ala62Thr	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>A	p.Ala49Thr	missense_variant	Exon 3 of 4	1	NM_032488.4	ENSP00000222032.4
CNFN	ENST00000597255.1	c.145G>A	p.Ala49Thr	missense_variant	Exon 4 of 5	1		ENSP00000469590.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.69	.;T
M_CAP	Uncertain	0.094	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.083
Sift	Benign	0.13	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.041	B;B
Vest4		0.64
MutPred		0.52		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.17
MPC		0.66
ClinPred		0.54	D
GERP RS		2.6
Varity_R		0.092
gMVP		0.66

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: rs1473289137; hg19: chr19-42891596;