chr17-41307713-G-C

Position:

• chr17-41307713-G-C

Variant summary

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

The NM_001146182.2(KRTAP16-1):​c.1541C>G​(p.Pro514Arg) 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: 33)
• Consequence: KRTAP16-1 NM_001146182.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11

Genes affected

KRTAP16-1 (HGNC:18916): (keratin associated protein 16-1) 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=0.16420439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP16-1	NM_001146182.2	c.1541C>G	p.Pro514Arg	missense_variant	1/1	ENST00000391352.2	NP_001139654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP16-1	ENST00000391352.2	c.1541C>G	p.Pro514Arg	missense_variant	1/1	6	NM_001146182.2	ENSP00000375147.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.1541C>G (p.P514R) alteration is located in exon 1 (coding exon 1) of the KRTAP16-1 gene. This alteration results from a C to G substitution at nucleotide position 1541, causing the proline (P) at amino acid position 514 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.095
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.25
MutPred		0.30		Gain of MoRF binding (P = 1e-04);
MVP		0.22
ClinPred		0.78	D
GERP RS		4.5
Varity_R		0.27
gMVP		0.076

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: chr17-39463965;