Variant 12-52237522-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000331817.6(KRT7):c.550A>C(p.Ile184Leu) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KRT7
ENST00000331817.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

Variant links:

Genes affected

KRT7 (HGNC:6445): (keratin 7) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins 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 type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

KRT7 links:

KRT7 (HGNC:):

KRT7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT7	NM_005556.4 linkuse as main transcript	c.550A>C	p.Ile184Leu	missense_variant	3/9	ENST00000331817.6	NP_005547.3	P08729
KRT7	XM_011538325.3 linkuse as main transcript	c.550A>C	p.Ile184Leu	missense_variant	3/8		XP_011536627.1
KRT7	XM_047428827.1 linkuse as main transcript	c.550A>C	p.Ile184Leu	missense_variant	3/7		XP_047284783.1
KRT7	XM_017019294.2 linkuse as main transcript	c.-130A>C		5_prime_UTR_variant	1/7		XP_016874783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT7	ENST00000331817.6 linkuse as main transcript	c.550A>C	p.Ile184Leu	missense_variant	3/9	1	NM_005556.4	ENSP00000329243.5		P08729
KRT7	ENST00000547613.1 linkuse as main transcript	n.255A>C		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152152

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000916

AC:

1328

AN:

1450558

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

597

AN XY:

721862

show subpopulations

Gnomad4 AFR exome

AF:

0.000903

Gnomad4 AMR exome

AF:

0.0000674

Gnomad4 ASJ exome

AF:

0.000308

Gnomad4 EAS exome

AF:

0.000380

Gnomad4 SAS exome

AF:

0.000350

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.000717

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74452

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Apr 23, 2024

The c.550A>C (p.I184L) alteration is located in exon 3 (coding exon 3) of the KRT7 gene. This alteration results from a A to C substitution at nucleotide position 550, causing the isoleucine (I) at amino acid position 184 to be replaced by a leucine (L). 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

Benign

0.24

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

Eigen

Benign

0.039

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

-0.090

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.51

Sift

Uncertain

0.015

Sift4G

Uncertain

0.056

Polyphen

0.83

Vest4

0.35

MutPred

0.59

Loss of catalytic residue at I184 (P = 0.0094);

MVP

0.62

MPC

0.34

ClinPred

0.47

GERP RS

3.6

Varity_R

0.28

gMVP

0.50

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