NM_182507.3:c.929G>T

Variant names:

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

Variant summary

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

The NM_182507.3(KRT80):​c.929G>T​(p.Arg310Leu) 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 1,460,386 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R310Q) has been classified as Uncertain significance.

• 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: 1.05
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Arg310Leu	missense	Exon 6 of 9	NP_872313.2	Q6KB66-1
	KRT80	NM_001081492.2		c.929G>T	p.Arg310Leu	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>T	p.Arg310Leu	missense	Exon 6 of 9	ENSP00000378292.2	Q6KB66-1
	KRT80	ENST00000313234.9	TSL:1	c.929G>T	p.Arg310Leu	missense	Exon 6 of 9	ENSP00000369361.2	Q6KB66-2
	KRT80	ENST00000466011.1	TSL:2	n.1085G>T		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460386 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726324

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

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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: 0.00000270 AC: 3 AN: 1110894

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.32	N
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.0
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.70
MutPred		0.55		Loss of MoRF binding (P = 0.0541)
MVP		0.69
MPC		0.60
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.58
gMVP		0.79
Mutation Taster		=67/33	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;