17-40928252-T-G

Variant names:

• chr17-40928252-T-G
• rs9257
• NM_015515.5:c.907A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015515.5(KRT23):​c.907A>C​(p.Thr303Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRT23 NM_015515.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 39 publications found

Genes affected

KRT23 (HGNC:6438): (keratin 23) The protein encoded by this gene is a member of the keratin family. The keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into cytokeratins and hair keratins. The type I cytokeratins consist of acidic proteins which are arranged in pairs of heterotypic keratin chains. The type I cytokeratin genes are clustered in a region of chromosome 17q12-q21. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ENSG00000234477 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19857883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT23	NM_015515.5	c.907A>C	p.Thr303Pro	missense_variant	Exon 6 of 9	ENST00000209718.8	NP_056330.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT23	ENST00000209718.8	c.907A>C	p.Thr303Pro	missense_variant	Exon 6 of 9	1	NM_015515.5	ENSP00000209718.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Uncertain	0.59	D;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.20	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		0.35
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.020	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.055	B;.
Vest4		0.22
MutPred		0.56		Loss of phosphorylation at T303 (P = 0.0418);.;
MVP		0.48
MPC		0.24
ClinPred		0.52	D
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.64

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: rs9257; hg19: chr17-39084504;