chr17-41054875-G-C

Variant names:

• chr17-41054875-G-C
• rs1256476644
• NM_033032.3:c.337C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033032.3(KRTAP2-2):​c.337C>G​(p.Pro113Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00010 (2 hom., cov: 15)
  • Exomes 𝑓: 0.000014 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP2-2 NM_033032.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.13
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05250573).

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.337C>G	p.Pro113Ala	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.337C>G	p.Pro113Ala	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
	ENSG00000306126	ENST00000815517.1		n.220-5424G>C		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-5424G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000104 AC: 10 AN: 96062 Hom.: 2 Cov.: 15

Gnomad AFR AF: 0.000548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000561 AC: 7 AN: 124874 AF XY: 0.0000447

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000143 AC: 19 AN: 1325562 Hom.: 4 Cov.: 32 AF XY: 0.0000123 AC XY: 8 AN XY: 651698

African (AFR) AF: 0.000602 AC: 15 AN: 24930

American (AMR) AF: 0.0000355 AC: 1 AN: 28166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23124

East Asian (EAS) AF: 0.0000310 AC: 1 AN: 32228

South Asian (SAS) AF: 0.00 AC: 0 AN: 69732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3894

European-Non Finnish (NFE) AF: 9.49e-7 AC: 1 AN: 1053226

Other (OTH) AF: 0.0000182 AC: 1 AN: 54936

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000104 AC: 10 AN: 96080 Hom.: 2 Cov.: 15 AF XY: 0.0000435 AC XY: 2 AN XY: 45986

African (AFR) AF: 0.000547 AC: 8 AN: 14628

American (AMR) AF: 0.000210 AC: 2 AN: 9544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2884

East Asian (EAS) AF: 0.00 AC: 0 AN: 3456

South Asian (SAS) AF: 0.00 AC: 0 AN: 2894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 222

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53062

Other (OTH) AF: 0.00 AC: 0 AN: 1338

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.7
DANN	Benign	0.86
DEOGEN2	Benign	0.00033	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Uncertain	0.055	T
Vest4		0.30
MutPred		0.34		Loss of glycosylation at P113 (P = 0.0566)
MVP		0.092
ClinPred		0.024	T
GERP RS		2.7
PromoterAI		-0.00010	Neutral
Varity_R		0.023
gMVP		0.029
Mutation Taster		=99/1	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: rs1256476644; hg19: chr17-39211127; COSMIC: COSV105929691; COSMIC: COSV105929691;