Variant 17-40982404-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001389244.1(KRT40):c.590G>C(p.Gly197Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

KRT40
NM_001389244.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.180

Variant links:

Genes affected

KRT40 (HGNC:26707): (keratin 40) This gene encodes a member of the type I (acidic) keratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. The type I keratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2009]

KRT40 links:

LOC107985072 (HGNC:):

LOC107985072 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.123805255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT40	NM_001389244.1 linkuse as main transcript	c.590G>C	p.Gly197Ala	missense_variant	3/7	ENST00000377755.9	NP_001376173.1
LOC107985072	XR_001752886.2 linkuse as main transcript	n.424C>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KRT40	ENST00000377755.9 linkuse as main transcript	c.590G>C	p.Gly197Ala	missense_variant	3/7	1	NM_001389244.1	ENSP00000366984	P1
KRT40	ENST00000398486.2 linkuse as main transcript	c.590G>C	p.Gly197Ala	missense_variant	5/9	1		ENSP00000381500	P1
KRT40	ENST00000684280.1 linkuse as main transcript	c.590G>C	p.Gly197Ala	missense_variant	5/9			ENSP00000506768	P1
KRT40	ENST00000461923.5 linkuse as main transcript	c.590G>C	p.Gly197Ala	missense_variant, NMD_transcript_variant	5/9	2		ENSP00000434458

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458592

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725610

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 02, 2022

The c.590G>C (p.G197A) alteration is located in exon 5 (coding exon 3) of the KRT40 gene. This alteration results from a G to C substitution at nucleotide position 590, causing the glycine (G) at amino acid position 197 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.19

M_CAP

Benign

0.079

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.29

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.026

B;B

Vest4

0.15

MutPred

0.50

Loss of catalytic residue at G197 (P = 0.126);Loss of catalytic residue at G197 (P = 0.126);

MVP

0.61

MPC

0.29

ClinPred

0.37

GERP RS

3.1

Varity_R

0.18

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over