chr17-41084312-A-G

Position:

• chr17-41084312-A-G

Variant summary

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

The NM_033061.4(KRTAP4-7):​c.106A>G​(p.Arg36Gly) 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. 12/18 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-7 NM_033061.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.638

Genes affected

KRTAP4-7 (HGNC:18898): (keratin associated protein 4-7) 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=0.28618586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-7	NM_033061.4	c.106A>G	p.Arg36Gly	missense_variant	1/1	ENST00000391417.6	NP_149050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP4-7	ENST00000391417.6	c.106A>G	p.Arg36Gly	missense_variant	1/1	6	NM_033061.4	ENSP00000375236.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461782 Hom.: 0 Cov.: 154 AF XY: 0.00 AC XY: 0 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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 26, 2024

The c.106A>G (p.R36G) alteration is located in exon 1 (coding exon 1) of the KRTAP4-7 gene. This alteration results from a A to G substitution at nucleotide position 106, causing the arginine (R) at amino acid position 36 to be replaced by a glycine (G). 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
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.67
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.090	.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.8	D;.
REVEL	Benign	0.083
Sift	Benign	0.055	T;.
Sift4G	Benign	0.086	T;T
Vest4		0.46
MutPred		0.48		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP		0.22
MPC		0.040
ClinPred		0.13	T
GERP RS		-1.1
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs1342840187; hg19: chr17-39240564;