17-41046978-G-T

Variant names:

• chr17-41046978-G-T
• rs1439869821
• NM_001123387.1:c.290C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001123387.1(KRTAP2-1):​c.290C>A​(p.Thr97Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP2-1 NM_001123387.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

Genes affected

KRTAP2-1 (HGNC:16775): (keratin associated protein 2-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000306126 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34802854).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123387.1. 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
	KRTAP2-1	NM_001123387.1	MANE Select	c.290C>A	p.Thr97Asn	missense	Exon 1 of 1	NP_001116859.1	Q9BYU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP2-1	ENST00000391419.3	TSL:6 MANE Select	c.290C>A	p.Thr97Asn	missense	Exon 1 of 1	ENSP00000375238.3	Q9BYU5
	ENSG00000306126	ENST00000815517.1		n.220-13321G>T		intron	N/A
	ENSG00000306126	ENST00000815518.1		n.160-13321G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152194 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000223 AC: 3 AN: 134412 AF XY: 0.0000137

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000125

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000188

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000224 AC: 31 AN: 1383850 Hom.: 0 Cov.: 33 AF XY: 0.0000293 AC XY: 20 AN XY: 682826

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

African (AFR) AF: 0.00 AC: 0 AN: 31542

American (AMR) AF: 0.00 AC: 0 AN: 35654

Ashkenazi Jewish (ASJ) AF: 0.000199 AC: 5 AN: 25100

East Asian (EAS) AF: 0.00 AC: 0 AN: 35780

South Asian (SAS) AF: 0.000240 AC: 19 AN: 79034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36424

Middle Eastern (MID) AF: 0.000246 AC: 1 AN: 4064

European-Non Finnish (NFE) AF: 0.00000464 AC: 5 AN: 1078528

Other (OTH) AF: 0.0000173 AC: 1 AN: 57724

⚠️ 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 AF: 0.0000197 AC: 3 AN: 152194 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

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

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

⚠️ 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: 0.0000960 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	0.23
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.049	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.42		Loss of glycosylation at T97 (P = 0.3064)
MVP		0.14
ClinPred		0.63	D
GERP RS		5.8
PromoterAI		0.0016	Neutral
Varity_R		0.18
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1439869821; hg19: chr17-39203230;