17-41084389-A-G

Position:

• chr17-41084389-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_033061.4(KRTAP4-7):​c.183A>G​(p.Gln61Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000087 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-7 NM_033061.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.10

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 17-41084389-A-G is Benign according to our data. Variant chr17-41084389-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.11 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP4-7	NM_033061.4	c.183A>G	p.Gln61Gln	synonymous_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.183A>G	p.Gln61Gln	synonymous_variant	1/1	6	NM_033061.4	ENSP00000375236.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 69 AN: 129554 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000221

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000233

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000494

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000125 AC: 31 AN: 248626 Hom.: 0 AF XY: 0.000111 AC XY: 15 AN XY: 135144

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000273

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000165

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000873 AC: 112 AN: 1282816 Hom.: 0 Cov.: 161 AF XY: 0.0000769 AC XY: 49 AN XY: 637558

Gnomad4 AFR exome AF: 0.00235

Gnomad4 AMR exome AF: 0.000197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000310

Gnomad4 SAS exome AF: 0.0000268

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000242

Gnomad4 OTH exome AF: 0.000316

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000571 AC: 74 AN: 129654 Hom.: 0 Cov.: 31 AF XY: 0.000474 AC XY: 30 AN XY: 63340

Gnomad4 AFR AF: 0.00205

Gnomad4 AMR AF: 0.000221

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000233

Gnomad4 NFE AF: 0.0000494

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00325 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

KRTAP4-7: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs867963353; hg19: chr17-39240641; COSMIC: COSV66951139;