17-40818903-G-T

Variant names:

• chr17-40818903-G-T
• rs368733857
• NM_000421.5:c.1632C>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000421.5(KRT10):​c.1632C>A​(p.Gly544Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,412,036 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (112 hom.)
• Consequence: KRT10 NM_000421.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.14
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-40818903-G-T is Benign according to our data. Variant chr17-40818903-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1335270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.14 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 11 AD,AR gene

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.1632C>A	p.Gly544Gly	synonymous	Exon 7 of 8	NP_000412.4
	KRT10	NM_001379366.1		c.1632C>A	p.Gly544Gly	synonymous	Exon 7 of 8	NP_001366295.1	A0A1B0GVI3
	KRT10-AS1	NR_160887.1		n.-242G>T		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.1632C>A	p.Gly544Gly	synonymous	Exon 7 of 8	ENSP00000269576.5	P13645
	KRT10	ENST00000635956.2	TSL:2	c.1632C>A	p.Gly544Gly	synonymous	Exon 7 of 8	ENSP00000490524.2	A0A1B0GVI3
	KRT10-AS1	ENST00000301665.10	TSL:2	n.-195G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00560 AC: 833 AN: 148664 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000867

Gnomad AMI AF: 0.00112

Gnomad AMR AF: 0.000932

Gnomad ASJ AF: 0.0105

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00194

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00769

Gnomad OTH AF: 0.00147

GnomAD2 exomes AF: 0.00883 AC: 891 AN: 100864 AF XY: 0.00885

Gnomad AFR exome AF: 0.00527

Gnomad AMR exome AF: 0.000447

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0291

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.00624

GnomAD4 exome AF: 0.00599 AC: 7569 AN: 1263266 Hom.: 112 Cov.: 31 AF XY: 0.00605 AC XY: 3774 AN XY: 624100

African (AFR) AF: 0.000614 AC: 15 AN: 24414

American (AMR) AF: 0.000634 AC: 17 AN: 26834

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 245 AN: 21830

East Asian (EAS) AF: 0.00 AC: 0 AN: 28958

South Asian (SAS) AF: 0.00302 AC: 198 AN: 65668

European-Finnish (FIN) AF: 0.0257 AC: 799 AN: 31110

Middle Eastern (MID) AF: 0.00100 AC: 5 AN: 4994

European-Non Finnish (NFE) AF: 0.00604 AC: 6081 AN: 1007464

Other (OTH) AF: 0.00402 AC: 209 AN: 51994

GnomAD4 genome AF: 0.00559 AC: 832 AN: 148770 Hom.: 11 Cov.: 32 AF XY: 0.00590 AC XY: 429 AN XY: 72682

African (AFR) AF: 0.000864 AC: 35 AN: 40496

American (AMR) AF: 0.000931 AC: 14 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.0105 AC: 36 AN: 3424

East Asian (EAS) AF: 0.00 AC: 0 AN: 5004

South Asian (SAS) AF: 0.00194 AC: 9 AN: 4636

European-Finnish (FIN) AF: 0.0219 AC: 221 AN: 10110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00768 AC: 513 AN: 66826

Other (OTH) AF: 0.00145 AC: 3 AN: 2062

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism

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: rs368733857; hg19: chr17-38975155;