chr17-41567350-T-G

Position:

• chr17-41567350-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000226.4(KRT9):​c.1795A>C​(p.Ser599Arg) 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. 14/21 in silico tools predict 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: KRT9 NM_000226.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.327

Genes affected

KRT9 (HGNC:6447): (keratin 9) This gene encodes the type I keratin 9, an intermediate filament chain expressed only in the terminally differentiated epidermis of palms and soles. Mutations in this gene cause epidermolytic palmoplantar keratoderma. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.22098246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT9	NM_000226.4	c.1795A>C	p.Ser599Arg	missense_variant	7/8	ENST00000246662.9	NP_000217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT9	ENST00000246662.9	c.1795A>C	p.Ser599Arg	missense_variant	7/8	1	NM_000226.4	ENSP00000246662.4
KRT9	ENST00000588431.1	c.1096A>C	p.Ser366Arg	missense_variant	8/9	1		ENSP00000467932.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 147

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epidermolytic palmoplantar keratoderma, 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 14, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.096	T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.25	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.18	N;.
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.98	D;.
Vest4		0.26
MutPred		0.28		Loss of phosphorylation at S599 (P = 0.0015);.;
MVP		0.91
MPC		0.078
ClinPred		0.65	D
GERP RS		0.65
Varity_R		0.15
gMVP		0.92

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.

Other links and lift over

hg19: chr17-39723602;