17-41034702-G-A

Position:

• chr17-41034702-G-A

Variant summary

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

The NM_030966.2(KRTAP1-3):​c.120C>T​(p.Cys40=) 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: not found (cov: 20)
  • Exomes 𝑓: 0.0000038 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP1-3 NM_030966.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

Genes affected

KRTAP1-3 (HGNC:16771): (keratin associated protein 1-3) 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 high sulfur KAP family and the gene is localized to a cluster of KAPs at 17q12-q21. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 17-41034702-G-A is Benign according to our data. Variant chr17-41034702-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTAP1-3	NM_030966.2	c.120C>T	p.Cys40=	synonymous_variant	1/1	ENST00000344363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTAP1-3	ENST00000344363.7	c.120C>T	p.Cys40=	synonymous_variant	1/1		NM_030966.2	P1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000385 AC: 5 AN: 1298738 Hom.: 0 Cov.: 33 AF XY: 0.00000462 AC XY: 3 AN XY: 649476

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: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000407

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

Alfa AF: 0.161 Hom.: 0

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

Sep 01, 2023

KRTAP1-3: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.1
DANN	Benign	0.86

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: rs75033421; hg19: chr17-39190954; COSMIC: COSV60335806; COSMIC: COSV60335806;