chr21-44573947-G-A

Position:

• chr21-44573947-G-A

Variant summary

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

The NM_198687.2(KRTAP10-4):​c.189G>A​(p.Val63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 151,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 47)
  • Exomes 𝑓: 0.0013 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP10-4 NM_198687.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.513

Genes affected

KRTAP10-4 (HGNC:20521): (keratin associated protein 10-4) This is an intronless gene located in a cluster of related genes on the q arm of chromosome 21. The proteins encoded by these genes form disulfide bonds with cysteine residues in hair keratins, thereby contributing to the structure and stability of hair fibers. [provided by RefSeq, Apr 2014]

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 21-44573947-G-A is Benign according to our data. Variant chr21-44573947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652763.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.513 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP10-4	NM_198687.2	c.189G>A	p.Val63=	synonymous_variant	1/1	ENST00000400374.4	NP_941960.2
TSPEAR	NM_144991.3	c.83-5942C>T		intron_variant		ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-122-5942C>T		intron_variant			NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP10-4	ENST00000400374.4	c.189G>A	p.Val63=	synonymous_variant	1/1		NM_198687.2	ENSP00000383225	P1
TSPEAR	ENST00000323084.9	c.83-5942C>T		intron_variant		1	NM_144991.3	ENSP00000321987	P1
TSPEAR	ENST00000642437.1	c.*28-5942C>T		intron_variant, NMD_transcript_variant				ENSP00000496535

Frequencies

GnomAD3 genomes AF: 0.00261 AC: 395 AN: 151132 Hom.: 0 Cov.: 47

Gnomad AFR AF: 0.00225

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000919

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00291

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.00145

GnomAD3 exomes AF: 0.00176 AC: 419 AN: 237396 Hom.: 3 AF XY: 0.00172 AC XY: 223 AN XY: 129586

Gnomad AFR exome AF: 0.0000740

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00414

Gnomad EAS exome AF: 0.00169

Gnomad SAS exome AF: 0.00388

Gnomad FIN exome AF: 0.00192

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.00169

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00127 AC: 1837 AN: 1449162 Hom.: 1 Cov.: 164 AF XY: 0.00136 AC XY: 979 AN XY: 719696

Gnomad4 AFR exome AF: 0.00178

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00472

Gnomad4 EAS exome AF: 0.000790

Gnomad4 SAS exome AF: 0.00274

Gnomad4 FIN exome AF: 0.00167

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00260 AC: 394 AN: 151252 Hom.: 0 Cov.: 47 AF XY: 0.00253 AC XY: 187 AN XY: 73884

Gnomad4 AFR AF: 0.00227

Gnomad4 AMR AF: 0.000918

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00291

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00537 Hom.: 1

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

Jun 01, 2023

KRTAP10-4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.8
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201222509; hg19: chr21-45993824;