17-41059741-C-T

Variant names:

• chr17-41059741-C-T
• rs1455642190
• NM_001165252.2:c.310G>A

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.310G>A​(p.Val104Met) 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP2-3 NM_001165252.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• 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=0.29713696).

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.310G>A	p.Val104Met	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.310G>A	p.Val104Met	missense	Exon 1 of 1	ENSP00000375237.2	P0C7H8
	ENSG00000306126	ENST00000815522.1		n.214C>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000306126	ENST00000815517.1		n.220-558C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1400794 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 691068

African (AFR) AF: 0.00 AC: 0 AN: 32104

American (AMR) AF: 0.00 AC: 0 AN: 35850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 36486

South Asian (SAS) AF: 0.00 AC: 0 AN: 79362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4518

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080728

Other (OTH) AF: 0.00 AC: 0 AN: 58006

GnomAD4 genome Cov.: 32

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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0030	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.9
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0050	D
Vest4		0.33
MutPred		0.52		Loss of glycosylation at S103 (P = 0.0426)
MVP		0.22
MPC		2.3
ClinPred		0.94	D
GERP RS		4.7
PromoterAI		0.019	Neutral
Varity_R		0.066
gMVP		0.056

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: rs1455642190; hg19: chr17-39215993;