NM_000421.5:c.1443A>C

Variant names:

• chr17-40819092-T-G
• rs879229899
• NM_000421.5:c.1443A>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000421.5(KRT10):​c.1443A>C​(p.Gly481Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,284,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRT10 NM_000421.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.22
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 17-40819092-T-G is Benign according to our data. Variant chr17-40819092-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3715047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.22 with no splicing effect.

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.1443A>C	p.Gly481Gly	synonymous	Exon 7 of 8	NP_000412.4
	KRT10	NM_001379366.1		c.1443A>C	p.Gly481Gly	synonymous	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3
	KRT10-AS1	NR_160886.1		n.-93T>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT10	ENST00000269576.6	TSL:1 MANE Select	c.1443A>C	p.Gly481Gly	synonymous	Exon 7 of 8	ENSP00000269576.5	P13645
	KRT10	ENST00000635956.2	TSL:2	c.1443A>C	p.Gly481Gly	synonymous	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
	KRT10-AS1	ENST00000436612.7	TSL:2	n.22T>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 4 AN: 121252 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000797

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000175

Gnomad OTH AF: 0.000603

GnomAD4 exome AF: 0.0000280 AC: 36 AN: 1284458 Hom.: 0 Cov.: 34 AF XY: 0.0000315 AC XY: 20 AN XY: 634180

African (AFR) AF: 0.0000772 AC: 2 AN: 25912

American (AMR) AF: 0.00 AC: 0 AN: 27002

Ashkenazi Jewish (ASJ) AF: 0.0000438 AC: 1 AN: 22828

East Asian (EAS) AF: 0.0000361 AC: 1 AN: 27676

South Asian (SAS) AF: 0.0000284 AC: 2 AN: 70392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4226

European-Non Finnish (NFE) AF: 0.0000264 AC: 27 AN: 1021554

Other (OTH) AF: 0.0000568 AC: 3 AN: 52806

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000330 AC: 4 AN: 121252 Hom.: 0 Cov.: 31 AF XY: 0.0000338 AC XY: 2 AN XY: 59246

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000321 AC: 1 AN: 31124

American (AMR) AF: 0.0000797 AC: 1 AN: 12550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2978

East Asian (EAS) AF: 0.00 AC: 0 AN: 3870

South Asian (SAS) AF: 0.00 AC: 0 AN: 3604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.0000175 AC: 1 AN: 57144

Other (OTH) AF: 0.000603 AC: 1 AN: 1658

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0741174), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00253 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.72
PhyloP100		-4.2

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

Other links and lift over

dbSNP: rs879229899; hg19: chr17-38975344;