chr11-71582572-T-C

Position:

• chr11-71582572-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005405.3(KRTAP5-11):​c.266A>G​(p.Lys89Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: KRTAP5-11 NM_001005405.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.220

Genes affected

KRTAP5-11 (HGNC:23606): (keratin associated protein 5-11) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-11 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049553275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-11	NM_001005405.3	c.266A>G	p.Lys89Arg	missense_variant	1/1	ENST00000398530.1	NP_001005405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-11	ENST00000398530.1	c.266A>G	p.Lys89Arg	missense_variant	1/1	6	NM_001005405.3	ENSP00000381541.1
KRTAP5-11	ENST00000526239.1	n.381-415A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74218

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2024

The c.266A>G (p.K89R) alteration is located in exon 1 (coding exon 1) of the KRTAP5-11 gene. This alteration results from a A to G substitution at nucleotide position 266, causing the lysine (K) at amino acid position 89 to be replaced by an arginine (R). 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	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.7
DANN	Benign	0.70
DEOGEN2	Benign	0.023	.;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	2.0	.;M
PROVEAN	Benign	0.79	.;N
REVEL	Benign	0.052
Sift	Benign	0.34	.;T
Sift4G	Benign	0.74	T;T
Polyphen		0.023	.;B
Vest4		0.10
MutPred		0.31		Loss of methylation at K89 (P = 2e-04);Loss of methylation at K89 (P = 2e-04);
MVP		0.13
MPC		0.011
ClinPred		0.071	T
GERP RS		2.3
Varity_R		0.037
gMVP		0.0066

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1161508337; hg19: chr11-71293618;