11-71582425-T-G

Position:

• chr11-71582425-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005405.3(KRTAP5-11):​c.413A>C​(p.Lys138Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KRTAP5-11 NM_001005405.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.199

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095948935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-11	NM_001005405.3	c.413A>C	p.Lys138Thr	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.413A>C	p.Lys138Thr	missense_variant	1/1	6	NM_001005405.3	ENSP00000381541.1
KRTAP5-11	ENST00000526239.1	n.381-268A>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 17, 2023

The c.413A>C (p.K138T) alteration is located in exon 1 (coding exon 1) of the KRTAP5-11 gene. This alteration results from a A to C substitution at nucleotide position 413, causing the lysine (K) at amino acid position 138 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.026	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.5	.;M
PROVEAN	Uncertain	-2.9	.;D
REVEL	Benign	0.059
Sift	Uncertain	0.0090	.;D
Sift4G	Benign	0.19	T;T
Polyphen		0.024	.;B
Vest4		0.17
MutPred		0.33		Loss of methylation at K138 (P = 3e-04);Loss of methylation at K138 (P = 3e-04);
MVP		0.14
MPC		0.011
ClinPred		0.20	T
GERP RS		0.53
Varity_R		0.15
gMVP		0.016

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71293471;