17-41054875-G-T

Variant names:

• chr17-41054875-G-T
• rs1256476644
• NM_033032.3:c.337C>A

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.337C>A​(p.Pro113Thr) 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. 15/19 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: 𝑓 0.0 (0 hom., cov: 15)
  • Failed GnomAD Quality Control
• Consequence: KRTAP2-2 NM_033032.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=0.15443647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3	c.337C>A	p.Pro113Thr	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.337C>A	p.Pro113Thr	missense_variant	Exon 1 of 1	6	NM_033032.3	ENSP00000381494.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 96062 Hom.: 0 Cov.: 15 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 96062 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 45946

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.3
DANN	Benign	0.87
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.16
Sift	Benign	0.28	T
Sift4G	Benign	0.23	T
Vest4		0.29
MutPred		0.34		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.072
ClinPred		0.12	T
GERP RS		2.7
Varity_R		0.039
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1256476644; hg19: chr17-39211127;