11-71582441-G-T

Position:

• chr11-71582441-G-T

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.397C>A​(p.Gln133Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: KRTAP5-11 NM_001005405.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.37

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=0.06594893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-11	NM_001005405.3	c.397C>A	p.Gln133Lys	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.397C>A	p.Gln133Lys	missense_variant	1/1	6	NM_001005405.3	ENSP00000381541.1
KRTAP5-11	ENST00000526239.1	n.381-284C>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727214

Gnomad4 AFR exome AF: 0.0000299

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: 0.00000899

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

Aug 28, 2024

The c.397C>A (p.Q133K) alteration is located in exon 1 (coding exon 1) of the KRTAP5-11 gene. This alteration results from a C to A substitution at nucleotide position 397, causing the glutamine (Q) at amino acid position 133 to be replaced by a lysine (K). 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	0.086
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.8
DANN	Benign	0.55
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.037	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.1	.;M
PROVEAN	Benign	-0.72	.;N
REVEL	Benign	0.074
Sift	Benign	0.21	.;T
Sift4G	Benign	0.49	T;T
Polyphen		0.029	.;B
Vest4		0.19
MutPred		0.22		Gain of methylation at Q133 (P = 5e-04);Gain of methylation at Q133 (P = 5e-04);
MVP		0.040
MPC		0.011
ClinPred		0.11	T
GERP RS		0.76
Varity_R		0.080
gMVP		0.014

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: chr11-71293487;