11-71548764-G-A

Variant names:

• chr11-71548764-G-A
• NM_005553.4:c.107G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005553.4(KRTAP5-9):​c.107G>A​(p.Cys36Tyr) 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. 12/19 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)
• Consequence: KRTAP5-9 NM_005553.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56

Genes affected

KRTAP5-9 (HGNC:23604): (keratin associated protein 5-9) Enables identical protein binding activity. Predicted to be involved in epidermis development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3167106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-9	NM_005553.4	c.107G>A	p.Cys36Tyr	missense_variant	Exon 1 of 1	ENST00000528743.4	NP_005544.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-9	ENST00000528743.4	c.107G>A	p.Cys36Tyr	missense_variant	Exon 1 of 1	6	NM_005553.4	ENSP00000431443.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107G>A (p.C36Y) alteration is located in exon 1 (coding exon 1) of the KRTAP5-9 gene. This alteration results from a G to A substitution at nucleotide position 107, causing the cysteine (C) at amino acid position 36 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.77
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.17
Eigen_PC	Benign	-0.076
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.00097	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PROVEAN	Pathogenic	-9.6	D
REVEL	Benign	0.062
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.013	D
Polyphen		0.98	D
Vest4		0.16
MutPred		0.37		Gain of glycosylation at S34 (P = 0.1666);
MVP		0.66
MPC		0.16
ClinPred		0.65	D
GERP RS		1.5
Varity_R		0.68

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: chr11-71259810;