NM_182507.3:c.886C>G

Variant names:

• chr12-52173109-G-C
• rs150267443
• NM_182507.3:c.886C>G

Variant summary

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

The NM_182507.3(KRT80):​c.886C>G​(p.Arg296Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,216 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: 0.0000021 (0 hom.)
• Consequence: KRT80 NM_182507.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

KRT80 (HGNC:27056): (keratin 80) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene's expression profile shows that it encodes a type II epithelial keratin, although structurally the encoded protein is more like a type II hair keratin. This protein is involved in cell differentiation, localizing near desmosomal plaques in earlier stages of differentiation but then dispersing throughout the cytoplasm in terminally differentiating cells. The type II keratins are clustered in a region of chromosome 12q13. Two transcript variants encoding two different fully functional isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

LINC00592 (HGNC:27474): (long intergenic non-protein coding RNA 592)

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, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT80	NM_182507.3	c.886C>G	p.Arg296Gly	missense_variant	Exon 6 of 9	ENST00000394815.3	NP_872313.2
KRT80	NM_001081492.2	c.886C>G	p.Arg296Gly	missense_variant	Exon 6 of 9		NP_001074961.1
KRT80	XM_005268676.4	c.991C>G	p.Arg331Gly	missense_variant	Exon 4 of 7		XP_005268733.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT80	ENST00000394815.3	c.886C>G	p.Arg296Gly	missense_variant	Exon 6 of 9	1	NM_182507.3	ENSP00000378292.2
KRT80	ENST00000313234.9	c.886C>G	p.Arg296Gly	missense_variant	Exon 6 of 9	1		ENSP00000369361.2
KRT80	ENST00000466011.1	n.1042C>G		non_coding_transcript_exon_variant	Exon 4 of 7	2
LINC00592	ENST00000640420.1	n.413+8158G>C		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250182 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461216 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726916

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: 0.00000270

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	0.54
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	.;D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.69
MutPred		0.63		Gain of catalytic residue at R296 (P = 0.0215);Gain of catalytic residue at R296 (P = 0.0215);
MVP		0.69
MPC		0.58
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.86
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs150267443; hg19: chr12-52566893;