rs552783643

Variant names:

• chr12-52173066-C-T
• rs552783643
• NM_182507.3:c.929G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-52173066-C-T
• chr12-52173066-C-A
• chr12-52173066-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_182507.3(KRT80):​c.929G>A​(p.Arg310Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,668 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (1 hom.)
• Consequence: KRT80 NM_182507.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10589275).

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.929G>A	p.Arg310Gln	missense	Exon 6 of 9	NP_872313.2	Q6KB66-1
	KRT80	NM_001081492.2		c.929G>A	p.Arg310Gln	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.929G>A	p.Arg310Gln	missense	Exon 6 of 9	ENSP00000378292.2	Q6KB66-1
	KRT80	ENST00000313234.9	TSL:1	c.929G>A	p.Arg310Gln	missense	Exon 6 of 9	ENSP00000369361.2	Q6KB66-2
	KRT80	ENST00000466011.1	TSL:2	n.1085G>A		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000399 AC: 10 AN: 250734 AF XY: 0.0000516

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

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: 0.0000260 AC: 38 AN: 1460386 Hom.: 1 Cov.: 31 AF XY: 0.0000358 AC XY: 26 AN XY: 726324

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.000179 AC: 8 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110894

Other (OTH) AF: 0.0000166 AC: 1 AN: 60326

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74464

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41548

American (AMR) AF: 0.00 AC: 0 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000145 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000330 AC: 4

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	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.47	N
PhyloP100		1.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.25
Sift	Benign	0.81	T
Sift4G	Benign	1.0	T
Polyphen		0.95	P
Vest4		0.30
MutPred		0.51		Gain of ubiquitination at K308 (P = 0.0399)
MVP		0.65
MPC		0.53
ClinPred		0.14	T
GERP RS		4.4
Varity_R		0.10
gMVP		0.63
Mutation Taster		=97/3	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: rs552783643; hg19: chr12-52566850; COSMIC: COSV57551725;