Variant 12-52567169-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_175053.4(KRT74):c.1391-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,426 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

KRT74
NM_175053.4 splice_acceptor, intron

Scores

Splicing: ADA: 0.9999

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 0.777

Variant links:

Genes affected

KRT74 (HGNC:28929): (keratin 74) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This protein belongs to a family of keratins that are specifically expressed in the inner root sheath of hair follicles.[provided by RefSeq, Jun 2009]

KRT74 links:

KRT74 (HGNC:):

KRT74 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;

PP5

Variant 12-52567169-C-T is Pathogenic according to our data. Variant chr12-52567169-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 66968.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT74	NM_175053.4 linkuse as main transcript	c.1391-1G>A		splice_acceptor_variant, intron_variant		ENST00000305620.3	NP_778223.2	Q7RTS7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
KRT74	ENST00000305620.3 linkuse as main transcript	c.1391-1G>A	splice_acceptor_variant, intron_variant	1	NM_175053.4	ENSP00000307240.2	Q7RTS7
KRT74	ENST00000549343.5 linkuse as main transcript	c.1433-1G>A	splice_acceptor_variant, intron_variant	5		ENSP00000447447.1	F8W1S1
KRT74	ENST00000546384.1 linkuse as main transcript	n.378-1G>A	splice_acceptor_variant, intron_variant	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1437426

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710986

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:

9.13e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal dominant wooly hair

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2011

- -

not provided

Other:1

not provided, no classification provided

literature only

Epithelial Biology; Institute of Medical Biology, Singapore

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.85

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.84

GERP RS

4.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.84

SpliceAI score (max)

0.96

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.82

Position offset: -11

DS_AL_spliceai

0.96

Position offset: -1

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