10-113589023-AT-TC

Variant names:

• chr10-113589023-AT-TC
• NM_198060.4:c.5144_5145delATinsGA
• NRAP p.Asp1715Gly

Variant summary

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

The NM_198060.4(NRAP):​c.5144_5145delATinsGA​(p.Asp1715Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRAP NM_198060.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.56
• Publications: 0 publications found

Genes affected

NRAP (HGNC:7988): (nebulin related anchoring protein) Predicted to enable actin filament binding activity and muscle alpha-actinin binding activity. Predicted to be involved in cardiac muscle thin filament assembly. Predicted to be located in fascia adherens; muscle tendon junction; and myofibril. Predicted to be active in Z disc. [provided by Alliance of Genome Resources, Apr 2022]

HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198060.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRAP	NM_198060.4	MANE Select	c.5144_5145delATinsGA	p.Asp1715Gly	missense	N/A	NP_932326.2
	HABP2	NM_004132.5	MANE Select	c.*654_*655delATinsTC		3_prime_UTR	Exon 13 of 13	NP_004123.1	Q14520-1
	NRAP	NM_001261463.2		c.5147_5148delATinsGA	p.Asp1716Gly	missense	N/A	NP_001248392.1	A0A0A0MRM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.5144_5145delATinsGA	p.Asp1715Gly	missense	N/A	ENSP00000353078.3	Q86VF7-1
	NRAP	ENST00000369358.8	TSL:1	c.5147_5148delATinsGA	p.Asp1716Gly	missense	N/A	ENSP00000358365.4	A0A0A0MRM2
	NRAP	ENST00000360478.7	TSL:1	c.5039_5040delATinsGA	p.Asp1680Gly	missense	N/A	ENSP00000353666.3	Q86VF7-4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-115348782;