Variant 12-52544713-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033448.3(KRT71):c.1391T>G(p.Val464Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,610,686 control chromosomes in the GnomAD database, including 194,453 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.38 ( 13953 hom., cov: 33)

Exomes 𝑓: 0.49 ( 180500 hom. )

Consequence

KRT71
NM_033448.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

KRT71 (HGNC:28927): (keratin 71) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

KRT71 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.0458344E-5).

BP6

Variant 12-52544713-A-C is Benign according to our data. Variant chr12-52544713-A-C is described in ClinVar as [Benign]. Clinvar id is 1283050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT71	NM_033448.3 link	c.1391T>G	p.Val464Gly	missense_variant	9/9	ENST00000267119.6	NP_258259.1	Q3SY84
KRT71	XM_047428197.1 link	c.1265T>G	p.Val422Gly	missense_variant	8/8		XP_047284153.1
KRT71	XM_017018749.2 link	c.1145T>G	p.Val382Gly	missense_variant	10/10		XP_016874238.1
KRT71	XM_047428196.1 link	c.1030-364T>G		intron_variant			XP_047284152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6 link	c.1391T>G	p.Val464Gly	missense_variant	9/9	1	NM_033448.3	ENSP00000267119.5		Q3SY84

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58503

AN:

151978

Hom.:

13960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.423

GnomAD3 exomes

AF:

0.457

AC:

111394

AN:

243974

Hom.:

27454

AF XY:

0.456

AC XY:

60513

AN XY:

132820

show subpopulations

Gnomad AFR exome

AF:

0.0826

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.511

Gnomad SAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.497

GnomAD4 exome

AF:

0.490

AC:

714100

AN:

1458590

Hom.:

180500

Cov.:

AF XY:

0.485

AC XY:

352250

AN XY:

725646

show subpopulations

Gnomad4 AFR exome

AF:

0.0788

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.579

Gnomad4 EAS exome

AF:

0.534

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.460

Gnomad4 NFE exome

AF:

0.513

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.385

AC:

58483

AN:

152096

Hom.:

13953

Cov.:

AF XY:

0.384

AC XY:

28523

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0932

Gnomad4 AMR

AF:

0.471

Gnomad4 ASJ

AF:

0.596

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.514

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.498

Hom.:

46486

Bravo

AF:

0.378

TwinsUK

AF:

0.498

AC:

1847

ALSPAC

AF:

0.499

AC:

1923

ESP6500AA

AF:

0.0952

AC:

414

ESP6500EA

AF:

0.481

AC:

4099

ExAC

AF:

0.429

AC:

51366

Asia WGS

AF:

0.358

AC:

1243

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.015

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.0087

MetaRNN

Benign

0.000050

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.9

PrimateAI

Benign

0.36

PROVEAN

Benign

5.1

REVEL

Benign

0.10

Sift

Benign

0.64

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.048

MPC

0.12

ClinPred

0.0050

GERP RS

2.6

Varity_R

0.066

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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