NM_198689.3:c.129_134delGCCCCC

Variant names:

• chr21-44600749-AGCCCCC-A
• rs36208679
• NM_198689.3:c.129_134delGCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_198689.3(KRTAP10-7):​c.129_134delGCCCCC​(p.Glu43_Pro45delinsAsp) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KRTAP10-7 NM_198689.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 8 publications found

Genes affected

KRTAP10-7 (HGNC:22970): (keratin associated protein 10-7) Enables identical protein binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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]

TSPEAR Gene-Disease associations (from GenCC):

• ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 98

  Inheritance: AR Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_198689.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP10-7	NM_198689.3	c.129_134delGCCCCC	p.Glu43_Pro45delinsAsp	disruptive_inframe_deletion	Exon 1 of 1	ENST00000609664.2	NP_941962.1
TSPEAR	NM_144991.3	c.83-32750_83-32745delGGGGGC		intron_variant	Intron 1 of 11	ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-122-32750_-122-32745delGGGGGC		intron_variant	Intron 2 of 12		NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP10-7	ENST00000609664.2	c.129_134delGCCCCC	p.Glu43_Pro45delinsAsp	disruptive_inframe_deletion	Exon 1 of 1	6	NM_198689.3	ENSP00000476821.1
TSPEAR	ENST00000323084.9	c.83-32750_83-32745delGGGGGC		intron_variant	Intron 1 of 11	1	NM_144991.3	ENSP00000321987.4
TSPEAR	ENST00000642437.1	n.*28-32750_*28-32745delGGGGGC		intron_variant	Intron 2 of 12			ENSP00000496535.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36208679; hg19: chr21-46020649;