17-41054974-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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 (★).

• 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21808732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP2-2	NM_033032.3	c.238T>A	p.Cys80Ser	missense_variant	Exon 1 of 1	ENST00000398477.1	NP_149021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP2-2	ENST00000398477.1	c.238T>A	p.Cys80Ser	missense_variant	Exon 1 of 1	6	NM_033032.3	ENSP00000381494.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 26 AN: 111876 Hom.: 0 Cov.: 14 FAILED QC

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

Gnomad4 AFR exome AF: 0.000487

Gnomad4 AMR exome AF: 0.00124

Gnomad4 ASJ exome AF: 0.00338

Gnomad4 EAS exome AF: 0.00102

Gnomad4 SAS exome AF: 0.00142

Gnomad4 FIN exome AF: 0.00530

Gnomad4 NFE exome AF: 0.00143

Gnomad4 OTH exome AF: 0.00206

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

Gnomad4 AFR AF: 0.0000693

Gnomad4 AMR AF: 0.000278

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000216

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000934

Gnomad4 NFE AF: 0.000266

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.238T>A (p.C80S) alteration is located in exon 1 (coding exon 1) of the KRTAP2-2 gene. This alteration results from a T to A substitution at nucleotide position 238, causing the cysteine (C) at amino acid position 80 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.52
Sift	Benign	0.11	T;T
Sift4G	Uncertain	0.029	D;T
Vest4		0.27
MutPred		0.53		Gain of glycosylation at T78 (P = 0.0439);Gain of glycosylation at T78 (P = 0.0439);
MVP		0.16
ClinPred		0.86	D
GERP RS		4.9
Varity_R		0.24
gMVP		0.038

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

Publications

LitVar

Other links and lift over

dbSNP: rs1392229639; hg19: chr17-39211226;