chr17-41054971-G-T

Variant names:

• chr17-41054971-G-T
• rs1296589829
• NM_033032.3:c.241C>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.241C>A​(p.Pro81Thr) 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 0.00033 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0025 (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: 2.13
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22468159).

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.241C>A	p.Pro81Thr	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.241C>A	p.Pro81Thr	missense	Exon 1 of 1	ENSP00000381494.1	Q9BYT5
	ENSG00000306126	ENST00000815517.1		n.220-5328G>T		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-5328G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000325 AC: 36 AN: 110628 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.0000705

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: 0.00126

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.000719

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00250 AC: 2510 AN: 1003450 Hom.: 0 Cov.: 18 AF XY: 0.00266 AC XY: 1326 AN XY: 498312

⚠️ 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: 24818

American (AMR) AF: 0.00183 AC: 52 AN: 28430

Ashkenazi Jewish (ASJ) AF: 0.00512 AC: 96 AN: 18738

East Asian (EAS) AF: 0.00148 AC: 51 AN: 34456

South Asian (SAS) AF: 0.00226 AC: 145 AN: 64206

European-Finnish (FIN) AF: 0.00957 AC: 276 AN: 28846

Middle Eastern (MID) AF: 0.00407 AC: 13 AN: 3196

European-Non Finnish (NFE) AF: 0.00227 AC: 1718 AN: 755858

Other (OTH) AF: 0.00316 AC: 142 AN: 44902

⚠️ 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: 0.000325 AC: 36 AN: 110714 Hom.: 0 Cov.: 14 AF XY: 0.000271 AC XY: 14 AN XY: 51578

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

African (AFR) AF: 0.0000702 AC: 2 AN: 28486

American (AMR) AF: 0.000282 AC: 3 AN: 10642

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: 3260

European-Finnish (FIN) AF: 0.00126 AC: 8 AN: 6366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.000384 AC: 20 AN: 52142

Other (OTH) AF: 0.000711 AC: 1 AN: 1406

⚠️ 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: 0.000448 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	0.29
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.20	T
Vest4		0.30
MutPred		0.47		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.16
ClinPred		0.97	D
GERP RS		3.9
PromoterAI		0.020	Neutral
Varity_R		0.19
gMVP		0.067
Mutation Taster		=78/22	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: rs1296589829; hg19: chr17-39211223;