dbSNP rs766129021: KRT10:p.Ser551_Gly556del (chr17-40818867-TCCGCCGCCGGAGCTGCTG-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_000421.5(KRT10):c.1650_1667delCAGCAGCTCCGGCGGCGG(p.Ser551_Gly556del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,535,728 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

KRT10
NM_000421.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.33

Publications

0 publications found

Variant links:

Genes affected

KRT10 (HGNC:6413): (keratin 10) This gene encodes a member of the type I (acidic) cytokeratin 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. Mutations in this gene are associated with epidermolytic hyperkeratosis. This gene is located within a cluster of keratin family members on chromosome 17q21. [provided by RefSeq, Jul 2008]

KRT10 links:

KRT10-AS1 (HGNC:28305): (KRT10 antisense RNA 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRT10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_000421.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000421.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT10	NM_000421.5	MANE Select	c.1650_1667delCAGCAGCTCCGGCGGCGG	p.Ser551_Gly556del	disruptive_inframe_deletion	Exon 7 of 8	NP_000412.4
	KRT10	NM_001379366.1		c.1650_1667delCAGCAGCTCCGGCGGCGG	p.Ser551_Gly556del	disruptive_inframe_deletion	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KRT10	ENST00000269576.6	TSL:1 MANE Select	c.1650_1667delCAGCAGCTCCGGCGGCGG	p.Ser551_Gly556del	disruptive_inframe_deletion	Exon 7 of 8	ENSP00000269576.5	P13645
KRT10	ENST00000635956.2	TSL:2	c.1650_1667delCAGCAGCTCCGGCGGCGG	p.Ser551_Gly556del	disruptive_inframe_deletion	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
KRT10-AS1	ENST00000301665.10	TSL:2	n.-230_-213delCCGCCGCCGGAGCTGCTG		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

145000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000762

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000680

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00101

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000123

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000167

AC:

AN:

191424

AF XY:

0.000157

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000721

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000130

Gnomad OTH exome

AF:

0.000439

GnomAD4 exome

AF:

0.000125

AC:

174

AN:

1390614

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

692368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29758

American (AMR)

AF:

0.000124

AC:

AN:

40280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24610

East Asian (EAS)

AF:

0.000591

AC:

AN:

35536

South Asian (SAS)

AF:

0.000125

AC:

AN:

79842

European-Finnish (FIN)

AF:

0.0000278

AC:

AN:

35968

Middle Eastern (MID)

AF:

0.000714

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.000104

AC:

112

AN:

1081606

Other (OTH)

AF:

0.000366

AC:

AN:

57412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000117

AC:

AN:

145114

Hom.:

Cov.:

AF XY:

0.0000846

AC XY:

AN XY:

70882

show subpopulations

African (AFR)

AF:

0.0000760

AC:

AN:

39484

American (AMR)

AF:

0.0000679

AC:

AN:

14732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3350

East Asian (EAS)

AF:

0.00101

AC:

AN:

4932

South Asian (SAS)

AF:

0.00

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.000123

AC:

AN:

65252

Other (OTH)

AF:

0.00

AC:

AN:

2018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000870

Hom.:

Bravo

AF:

0.000178

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=197/3

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over