rs1375582289

Variant names:

• chr17-41054972-G-C
• rs1375582289
• NM_033032.3:c.240C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-41054972-G-C
• chr17-41054972-G-A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_033032.3(KRTAP2-2):​c.240C>G​(p.Cys80Trp) variant causes a missense change. 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. C80S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0022 (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: 3.81
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34756345).

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.240C>G	p.Cys80Trp	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.240C>G	p.Cys80Trp	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
	ENSG00000306126	ENST00000815517.1		n.220-5327G>C		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-5327G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 32 AN: 110882 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.0000703

Gnomad AMI AF: 0.00140

Gnomad AMR AF: 0.000282

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000217

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000325

Gnomad OTH AF: 0.000713

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00217 AC: 2173 AN: 1003458 Hom.: 0 Cov.: 17 AF XY: 0.00229 AC XY: 1140 AN XY: 498214

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

African (AFR) AF: 0.000685 AC: 17 AN: 24814

American (AMR) AF: 0.00172 AC: 49 AN: 28420

Ashkenazi Jewish (ASJ) AF: 0.00443 AC: 83 AN: 18730

East Asian (EAS) AF: 0.00134 AC: 46 AN: 34448

South Asian (SAS) AF: 0.00187 AC: 120 AN: 64138

European-Finnish (FIN) AF: 0.00803 AC: 231 AN: 28762

Middle Eastern (MID) AF: 0.00344 AC: 11 AN: 3194

European-Non Finnish (NFE) AF: 0.00197 AC: 1488 AN: 756092

Other (OTH) AF: 0.00285 AC: 128 AN: 44860

⚠️ 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: 0.000288 AC: 32 AN: 110966 Hom.: 0 Cov.: 14 AF XY: 0.000232 AC XY: 12 AN XY: 51704

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

African (AFR) AF: 0.0000700 AC: 2 AN: 28566

American (AMR) AF: 0.000281 AC: 3 AN: 10666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2834

East Asian (EAS) AF: 0.000217 AC: 1 AN: 4598

South Asian (SAS) AF: 0.00 AC: 0 AN: 3274

European-Finnish (FIN) AF: 0.00110 AC: 7 AN: 6356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.000325 AC: 17 AN: 52278

Other (OTH) AF: 0.000705 AC: 1 AN: 1418

⚠️ 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.

Alfa AF: 0.000122 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	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0060	D
Vest4		0.34
MutPred		0.56		Gain of glycosylation at T78 (P = 0.0612)
MVP		0.46
ClinPred		0.99	D
GERP RS		5.0
PromoterAI		0.0096	Neutral
Varity_R		0.45
gMVP		0.050
Mutation Taster		=48/52	disease causing

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: rs1375582289; hg19: chr17-39211224;