NM_033032.3:c.254C>T

Variant names:

• chr17-41054958-G-A
• rs1300239928
• NM_033032.3:c.254C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033032.3(KRTAP2-2):​c.254C>T​(p.Thr85Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 12)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP2-2 NM_033032.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98
• Publications: 0 publications found

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]

ENSG00000306126 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22077006).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033032.3. 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
	KRTAP2-2	NM_033032.3	MANE Select	c.254C>T	p.Thr85Met	missense	Exon 1 of 1	NP_149021.2	Q9BYT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-2	ENST00000398477.1	TSL:6 MANE Select	c.254C>T	p.Thr85Met	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
	ENSG00000306126	ENST00000815517.1		n.220-5341G>A		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-5341G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 12

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1008636 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 500774

African (AFR) AF: 0.00 AC: 0 AN: 25330

American (AMR) AF: 0.00 AC: 0 AN: 30146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18884

East Asian (EAS) AF: 0.00 AC: 0 AN: 34260

South Asian (SAS) AF: 0.00 AC: 0 AN: 64754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3166

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 758850

Other (OTH) AF: 0.00 AC: 0 AN: 44920

GnomAD4 genome Cov.: 12

Alfa AF: 0.00 Hom.: 0

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	0.095
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.073
Sift	Benign	0.10	T
Sift4G	Benign	0.20	T
Vest4		0.34
MutPred		0.27		Loss of sheet (P = 0.0457)
MVP		0.20
ClinPred		0.81	D
GERP RS		4.5
PromoterAI		0.0068	Neutral
Varity_R		0.040
gMVP		0.059

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: rs1300239928; hg19: chr17-39211210;