12-52171710-C-T

Variant names:

• chr12-52171710-C-T
• rs770804000
• NM_182507.3:c.1182G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_182507.3(KRT80):​c.1182G>A​(p.Met394Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,167,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000023 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: KRT80 NM_182507.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182507.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT80	NM_182507.3	MANE Select	c.1182G>A	p.Met394Ile	missense	Exon 8 of 9	NP_872313.2	Q6KB66-1
	KRT80	NM_001081492.2		c.1182G>A	p.Met394Ile	missense	Exon 8 of 9	NP_001074961.1	Q6KB66-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT80	ENST00000394815.3	TSL:1 MANE Select	c.1182G>A	p.Met394Ile	missense	Exon 8 of 9	ENSP00000378292.2	Q6KB66-1
	KRT80	ENST00000313234.9	TSL:1	c.1182G>A	p.Met394Ile	missense	Exon 8 of 9	ENSP00000369361.2	Q6KB66-2
	KRT80	ENST00000466011.1	TSL:2	n.1338G>A		non_coding_transcript_exon	Exon 6 of 7

Frequencies

GnomAD3 genomes AF: 0.0000227 AC: 3 AN: 131918 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000232

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000594 AC: 9 AN: 151504 AF XY: 0.0000500

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000232 AC: 24 AN: 1035272 Hom.: 0 Cov.: 30 AF XY: 0.0000195 AC XY: 10 AN XY: 514028

African (AFR) AF: 0.00 AC: 0 AN: 23854

American (AMR) AF: 0.000683 AC: 20 AN: 29292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18698

East Asian (EAS) AF: 0.00 AC: 0 AN: 26770

South Asian (SAS) AF: 0.0000144 AC: 1 AN: 69504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 780518

Other (OTH) AF: 0.0000720 AC: 3 AN: 41660

GnomAD4 genome AF: 0.0000227 AC: 3 AN: 131918 Hom.: 0 Cov.: 24 AF XY: 0.0000157 AC XY: 1 AN XY: 63592

African (AFR) AF: 0.00 AC: 0 AN: 35000

American (AMR) AF: 0.000232 AC: 3 AN: 12946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3184

East Asian (EAS) AF: 0.00 AC: 0 AN: 4360

South Asian (SAS) AF: 0.00 AC: 0 AN: 3686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61700

Other (OTH) AF: 0.00 AC: 0 AN: 1844

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000889 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.0	L
PhyloP100		2.8
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.43	N
REVEL	Uncertain	0.41
Sift	Benign	0.11	T
Sift4G	Benign	0.31	T
Polyphen		0.95	P
Vest4		0.44
MutPred		0.36		Gain of catalytic residue at R393 (P = 0.0211)
MVP		0.74
MPC		0.34
ClinPred		0.12	T
GERP RS		4.7
Varity_R		0.31
gMVP		0.50
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs770804000; hg19: chr12-52565494;