Variant 12-52590927-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_080747.3(KRT72):c.998G>A(p.Gly333Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,453,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

KRT72
NM_080747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

Variant links:

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]

KRT72 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT72	NM_080747.3 linkuse as main transcript	c.998G>A	p.Gly333Glu	missense_variant	6/9	ENST00000293745.7	NP_542785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT72	ENST00000293745.7 linkuse as main transcript	c.998G>A	p.Gly333Glu	missense_variant	6/9	1	NM_080747.3	ENSP00000293745	P1	Q14CN4-1
KRT72	ENST00000537672.6 linkuse as main transcript	c.998G>A	p.Gly333Glu	missense_variant	6/10	2		ENSP00000441160	P1	Q14CN4-1
KRT72	ENST00000354310.4 linkuse as main transcript	c.963+537G>A		intron_variant		2		ENSP00000346269		Q14CN4-3
KRT72	ENST00000550829.1 linkuse as main transcript	c.*687G>A		3_prime_UTR_variant, NMD_transcript_variant	7/10	2		ENSP00000446881

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000963

AC:

AN:

1453484

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

722570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2022

The c.998G>A (p.G333E) alteration is located in exon 6 (coding exon 6) of the KRT72 gene. This alteration results from a G to A substitution at nucleotide position 998, causing the glycine (G) at amino acid position 333 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-7.4

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.032

D;D

Polyphen

1.0

D;D

Vest4

0.53

MutPred

0.65

Gain of catalytic residue at A329 (P = 0.0266);Gain of catalytic residue at A329 (P = 0.0266);

MVP

0.67

MPC

0.35

ClinPred

0.99

GERP RS

5.1

Varity_R

0.65

gMVP

0.45

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over