rs1392229639

Variant names:

• chr17-41054974-A-T
• rs1392229639
• NM_033032.3:c.238T>A

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.238T>A​(p.Cys80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. C80W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0016 (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: 1.31
• 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=0.21808732).

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.238T>A	p.Cys80Ser	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.238T>A	p.Cys80Ser	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
	ENSG00000306126	ENST00000815517.1		n.220-5325A>T		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-5325A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000232 AC: 26 AN: 111876 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.0000696

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000279

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000215

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000934

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000266

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00156 AC: 1559 AN: 998314 Hom.: 0 Cov.: 17 AF XY: 0.00165 AC XY: 817 AN XY: 495846

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000487 AC: 12 AN: 24628

American (AMR) AF: 0.00124 AC: 35 AN: 28330

Ashkenazi Jewish (ASJ) AF: 0.00338 AC: 63 AN: 18648

East Asian (EAS) AF: 0.00102 AC: 35 AN: 34414

South Asian (SAS) AF: 0.00142 AC: 91 AN: 64064

European-Finnish (FIN) AF: 0.00530 AC: 152 AN: 28662

Middle Eastern (MID) AF: 0.00189 AC: 6 AN: 3180

European-Non Finnish (NFE) AF: 0.00143 AC: 1073 AN: 751744

Other (OTH) AF: 0.00206 AC: 92 AN: 44644

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000232 AC: 26 AN: 111956 Hom.: 0 Cov.: 14 AF XY: 0.000191 AC XY: 10 AN XY: 52228

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000693 AC: 2 AN: 28864

American (AMR) AF: 0.000278 AC: 3 AN: 10778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2856

East Asian (EAS) AF: 0.000216 AC: 1 AN: 4630

South Asian (SAS) AF: 0.00 AC: 0 AN: 3284

European-Finnish (FIN) AF: 0.000934 AC: 6 AN: 6426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.000266 AC: 14 AN: 52708

Other (OTH) AF: 0.00 AC: 0 AN: 1416

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.0091	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.52
Sift	Benign	0.11	T
Sift4G	Uncertain	0.029	D
Vest4		0.27
MutPred		0.53		Gain of glycosylation at T78 (P = 0.0439)
MVP		0.16
ClinPred		0.86	D
GERP RS		4.9
PromoterAI		-0.013	Neutral
Varity_R		0.24
gMVP		0.038
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1392229639; hg19: chr17-39211226;