17-41059827-C-A

Variant names:

• chr17-41059827-C-A
• rs1173910172
• NM_001165252.2:c.224G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001165252.2(KRTAP2-3):​c.224G>T​(p.Arg75Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRTAP2-3 NM_001165252.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.847
• Publications: 0 publications found

Genes affected

KRTAP2-3 (HGNC:18906): (keratin associated protein 2-3) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000306126 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2898363).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165252.2. 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
	KRTAP2-3	NM_001165252.2	MANE Select	c.224G>T	p.Arg75Leu	missense	Exon 1 of 1	NP_001158724.1	P0C7H8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-3	ENST00000391418.3	TSL:6 MANE Select	c.224G>T	p.Arg75Leu	missense	Exon 1 of 1	ENSP00000375237.2	P0C7H8
	ENSG00000306126	ENST00000815517.1		n.220-472C>A		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-472C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.85
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Vest4		0.38
MutPred		0.67		Loss of phosphorylation at T78 (P = 0.0619)
MVP		0.30
MPC		2.5
ClinPred		0.98	D
GERP RS		2.3
PromoterAI		0.021	Neutral
Varity_R		0.19
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1173910172; hg19: chr17-39216079;