rs377327186

Variant names:

• chr12-52172294-C-A
• rs377327186
• NM_182507.3:c.1082G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-52172294-C-A
• chr12-52172294-C-G
• chr12-52172294-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182507.3(KRT80):​c.1082G>T​(p.Arg361Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R361Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT80 NM_182507.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16789272).

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.1082G>T	p.Arg361Leu	missense	Exon 7 of 9	NP_872313.2	Q6KB66-1
	KRT80	NM_001081492.2		c.1082G>T	p.Arg361Leu	missense	Exon 7 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.1082G>T	p.Arg361Leu	missense	Exon 7 of 9	ENSP00000378292.2	Q6KB66-1
	KRT80	ENST00000313234.9	TSL:1	c.1082G>T	p.Arg361Leu	missense	Exon 7 of 9	ENSP00000369361.2	Q6KB66-2
	KRT80	ENST00000466011.1	TSL:2	n.1238G>T		non_coding_transcript_exon	Exon 5 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	2.8
DANN	Benign	0.94
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.014
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.058	T
Polyphen		0.0030	B
Vest4		0.25
MutPred		0.67		Loss of MoRF binding (P = 0.0061)
MVP		0.23
MPC		0.14
ClinPred		0.22	T
GERP RS		-0.79
Varity_R		0.27
gMVP		0.44
Mutation Taster		=85/15	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: rs377327186; hg19: chr12-52566078; COSMIC: COSV100502701;