17-41307905-C-A

Variant names:

• chr17-41307905-C-A
• rs188300014
• NM_001146182.2:c.1349G>T

Variant summary

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

The NM_001146182.2(KRTAP16-1):​c.1349G>T​(p.Arg450Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R450C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRTAP16-1 NM_001146182.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 0 publications found

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]

ENSG00000307895 (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=0.11805397).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146182.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP16-1	NM_001146182.2	MANE Select	c.1349G>T	p.Arg450Leu	missense	Exon 1 of 1	NP_001139654.1	A8MUX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP16-1	ENST00000391352.2	TSL:6 MANE Select	c.1349G>T	p.Arg450Leu	missense	Exon 1 of 1	ENSP00000375147.1	A8MUX0
	ENSG00000307895	ENST00000829650.1		n.679-17112G>T		intron	N/A
	ENSG00000307895	ENST00000829651.1		n.333-4631G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398344 Hom.: 0 Cov.: 38 AF XY: 0.00000290 AC XY: 2 AN XY: 689678

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078968

Other (OTH) AF: 0.00 AC: 0 AN: 58018

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.15
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.067
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.036	D
Vest4		0.17
MutPred		0.34		Loss of phosphorylation at S452 (P = 0.0533)
MVP		0.35
ClinPred		0.36	T
GERP RS		3.3
Varity_R		0.084
gMVP		0.092

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: rs188300014; hg19: chr17-39464157;