chr19-42387387-C-T

Variant names:

• chr19-42387387-C-T
• NM_032488.4:c.202G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032488.4(CNFN):​c.202G>A​(p.Gly68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CNFN NM_032488.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24746394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNFN	NM_032488.4	c.202G>A	p.Gly68Ser	missense_variant	Exon 3 of 4	ENST00000222032.10	NP_115877.2
CNFN	XM_005259332.4	c.241G>A	p.Gly81Ser	missense_variant	Exon 4 of 5		XP_005259389.1
CNFN	XM_011527396.3	c.241G>A	p.Gly81Ser	missense_variant	Exon 4 of 5		XP_011525698.1
CNFN	XM_011527397.3	c.241G>A	p.Gly81Ser	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.202G>A	p.Gly68Ser	missense_variant	Exon 3 of 4	1	NM_032488.4	ENSP00000222032.4
CNFN	ENST00000597255.1	c.202G>A	p.Gly68Ser	missense_variant	Exon 4 of 5	1		ENSP00000469590.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448972 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 719960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000232

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: 9.03e-7

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	Benign	0.15
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.032
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.83	N;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	1.4	N;.
REVEL	Benign	0.089
Sift	Benign	1.0	T;.
Sift4G	Benign	0.97	T;T
Polyphen		0.82	P;P
Vest4		0.43
MutPred		0.48		Gain of glycosylation at G68 (P = 0.0341);Gain of glycosylation at G68 (P = 0.0341);
MVP		0.29
MPC		0.39
ClinPred		0.65	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.60

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: chr19-42891539;