chr17-41117831-C-G

Position:

• chr17-41117831-C-G

Variant summary

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

The NM_033059.4(KRTAP4-11):​c.485G>C​(p.Arg162Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KRTAP4-11 NM_033059.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0680

Genes affected

KRTAP4-11 (HGNC:18911): (keratin associated protein 4-11) This protein is a member of the keratin-associated protein (KAP) family. The KAP proteins form a matrix of keratin intermediate filaments which contribute to the structure of hair fibers. KAP family members appear to have unique, family-specific amino- and carboxyl-terminal regions and are subdivided into three multi-gene families according to amino acid composition: the high sulfur, the ultrahigh sulfur, and the high tyrosine/glycine KAPs. This protein is a member of the ultrahigh sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Mar 2009]

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=0.352148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-11	NM_033059.4	c.485G>C	p.Arg162Pro	missense_variant	1/1	ENST00000391413.4	NP_149048.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-11	ENST00000391413.4	c.485G>C	p.Arg162Pro	missense_variant	1/1	6	NM_033059.4	ENSP00000375232.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454224 Hom.: 0 Cov.: 175 AF XY: 0.00000553 AC XY: 4 AN XY: 722944

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: 0.0000350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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

Nov 19, 2024

The c.485G>C (p.R162P) alteration is located in exon 1 (coding exon 1) of the KRTAP4-11 gene. This alteration results from a G to C substitution at nucleotide position 485, causing the arginine (R) at amino acid position 162 to be replaced by a proline (P). 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	0.26
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.0086	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.16
Sift	Benign	0.27	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.49		Gain of catalytic residue at R162 (P = 0.0985);
MVP		0.35
MPC		0.0082
ClinPred		0.81	D
GERP RS		4.3
Varity_R		0.45
gMVP		0.052

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: chr17-39274083;