Variant 17-41438594-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006771.4(KRT38):c.917A>C(p.Asp306Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 1,614,048 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 3 hom. )

Consequence

KRT38
NM_006771.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.179

Variant links:

Genes affected

KRT38 (HGNC:6456): (keratin 38) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

KRT38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028747618).

BP6

Variant 17-41438594-T-G is Benign according to our data. Variant chr17-41438594-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647767.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT38	NM_006771.4 linkuse as main transcript	c.917A>C	p.Asp306Ala	missense_variant	5/7	ENST00000246646.4	NP_006762.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT38	ENST00000246646.4 linkuse as main transcript	c.917A>C	p.Asp306Ala	missense_variant	5/7	1	NM_006771.4	ENSP00000246646	P1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00118

AC:

296

AN:

251410

Hom.:

AF XY:

0.00107

AC XY:

145

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.000624

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000856

AC:

1252

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

625

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.00361

Gnomad4 NFE exome

AF:

0.000629

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00105

AC:

160

AN:

152178

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000792

Hom.:

Bravo

AF:

0.000948

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00114

AC:

138

EpiCase

AF:

0.000872

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

KRT38: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

2.5

DANN

Benign

0.87

DEOGEN2

Benign

0.24

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.022

M_CAP

Benign

0.018

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

2.1

REVEL

Benign

0.20

Sift

Benign

0.14

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.061

MVP

0.26

MPC

0.046

ClinPred

0.0049

GERP RS

-7.0

Varity_R

0.050

gMVP

0.058

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