17-41055153-C-A

Variant names:

• chr17-41055153-C-A
• NM_033032.3:c.59G>T

Variant summary

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

The NM_033032.3(KRTAP2-2):​c.59G>T​(p.Cys20Phe) 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. 12/20 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: 19)
• Consequence: KRTAP2-2 NM_033032.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.146

Genes affected

KRTAP2-2 (HGNC:18905): (keratin associated protein 2-2) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15950239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3	c.59G>T	p.Cys20Phe	missense_variant	Exon 1 of 1	ENST00000398477.1	NP_149021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP2-2	ENST00000398477.1	c.59G>T	p.Cys20Phe	missense_variant	Exon 1 of 1	6	NM_033032.3	ENSP00000381494.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.59G>T (p.C20F) alteration is located in exon 1 (coding exon 1) of the KRTAP2-2 gene. This alteration results from a G to T substitution at nucleotide position 59, causing the cysteine (C) at amino acid position 20 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-7.6	D;D
REVEL	Benign	0.14
Sift	Benign	0.087	T;T
Sift4G	Uncertain	0.020	D;D
Vest4		0.18
MutPred		0.45		Gain of loop (P = 0.3485);Gain of loop (P = 0.3485);
MVP		0.46
ClinPred		0.69	D
GERP RS		-2.4
Varity_R		0.33
gMVP		0.11

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: chr17-39211405;