chr12-52592403-T-A

Variant names:

• chr12-52592403-T-A
• rs12833456
• NM_080747.3:c.791A>T

Variant summary

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

The NM_080747.3(KRT72):​c.791A>T​(p.Tyr264Phe) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRT72 NM_080747.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372
• Publications: 0 publications found

Genes affected

KRT72 (HGNC:28932): (keratin 72) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells. The type II keratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This gene encodes a type II keratin that is specifically expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q12-q13. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2009]

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=0.15611738).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080747.3. 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
	KRT72	NM_080747.3	MANE Select	c.791A>T	p.Tyr264Phe	missense	Exon 4 of 9	NP_542785.1	Q14CN4-1
	KRT72	NM_001146225.2		c.791A>T	p.Tyr264Phe	missense	Exon 4 of 10	NP_001139697.1	Q14CN4-1
	KRT72	NM_001146226.2		c.791A>T	p.Tyr264Phe	missense	Exon 4 of 8	NP_001139698.1	Q14CN4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT72	ENST00000293745.7	TSL:1 MANE Select	c.791A>T	p.Tyr264Phe	missense	Exon 4 of 9	ENSP00000293745.2	Q14CN4-1
	KRT72	ENST00000537672.6	TSL:2	c.791A>T	p.Tyr264Phe	missense	Exon 4 of 10	ENSP00000441160.2	Q14CN4-1
	KRT72	ENST00000354310.4	TSL:2	c.791A>T	p.Tyr264Phe	missense	Exon 4 of 8	ENSP00000346269.4	Q14CN4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.030	D
MutationAssessor	Benign	0.74	N
PhyloP100		0.37
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.20
Sift	Benign	0.28	T
Sift4G	Benign	0.27	T
Polyphen		0.0020	B
Vest4		0.30
MutPred		0.50		Gain of catalytic residue at I268 (P = 0)
MVP		0.58
MPC		0.047
ClinPred		0.12	T
GERP RS		3.7
Varity_R		0.18
gMVP		0.19
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12833456; hg19: chr12-52986187;