rs150267443

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-52173109-G-A
• chr12-52173109-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_182507.3(KRT80):​c.886C>T​(p.Arg296Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,398 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (2 hom., cov: 33)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: KRT80 NM_182507.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.886C>T	p.Arg296Cys	missense	Exon 6 of 9	NP_872313.2	Q6KB66-1
	KRT80	NM_001081492.2		c.886C>T	p.Arg296Cys	missense	Exon 6 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.886C>T	p.Arg296Cys	missense	Exon 6 of 9	ENSP00000378292.2	Q6KB66-1
	KRT80	ENST00000313234.9	TSL:1	c.886C>T	p.Arg296Cys	missense	Exon 6 of 9	ENSP00000369361.2	Q6KB66-2
	KRT80	ENST00000466011.1	TSL:2	n.1042C>T		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152182 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.0000680 AC: 17 AN: 250182 AF XY: 0.0000443

Gnomad AFR exome AF: 0.000433

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000985

GnomAD4 exome AF: 0.0000582 AC: 85 AN: 1461216 Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42 AN XY: 726916

African (AFR) AF: 0.000149 AC: 5 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39682

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5714

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111700

Other (OTH) AF: 0.00101 AC: 61 AN: 60358

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152182 Hom.: 2 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74344

African (AFR) AF: 0.000241 AC: 10 AN: 41442

American (AMR) AF: 0.00124 AC: 19 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00143 AC: 3 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.000185

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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	Benign	0.29
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.3
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.70
MPC		0.22
ClinPred		0.34	T
GERP RS		3.3
Varity_R		0.62
gMVP		0.69
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs150267443; hg19: chr12-52566893; COSMIC: COSV104619794;