11-1697547-G-A

Position:

• chr11-1697547-G-A

Variant summary

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

The NM_001012416.1(KRTAP5-6):​c.302G>A​(p.Gly101Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP5-6 NM_001012416.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.889

Genes affected

KRTAP5-6 (HGNC:23600): (keratin associated protein 5-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.046791583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP5-6	NM_001012416.1	c.302G>A	p.Gly101Glu	missense_variant	1/1	ENST00000382160.1	NP_001012416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP5-6	ENST00000382160.1	c.302G>A	p.Gly101Glu	missense_variant	1/1		NM_001012416.1	ENSP00000371595	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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 12, 2023

The c.302G>A (p.G101E) alteration is located in exon 1 (coding exon 1) of the KRTAP5-6 gene. This alteration results from a G to A substitution at nucleotide position 302, causing the glycine (G) at amino acid position 101 to be replaced by a glutamic acid (E). 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	0.23
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.5
DANN	Benign	0.40
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0095	N
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.3	M
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.030	N
REVEL	Benign	0.054
Sift4G	Benign	0.38	T
Polyphen		0.16	B
Vest4		0.26
MutPred		0.10		Loss of glycosylation at S98 (P = 0.1256);
MVP		0.16
MPC		0.016
ClinPred		0.15	T
GERP RS		-3.5
Varity_R		0.090
gMVP		0.010

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr11-1718777;