9-129637868-GAC-AAG

Variant names:

• chr9-129637868-GAC-AAG
• NM_017873.4:c.1186_1188delGTCinsCTT
• ASB6 p.Val396Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_017873.4(ASB6):​c.1186_1188delGTCinsCTT​(p.Val396Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: ASB6 NM_017873.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.45
• Publications: 0 publications found

Genes affected

ASB6 (HGNC:17181): (ankyrin repeat and SOCS box containing 6) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box, similar to the F-box, acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017873.4. 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
	ASB6	NM_017873.4	MANE Select	c.1186_1188delGTCinsCTT	p.Val396Leu	missense	N/A	NP_060343.1	Q9NWX5-1
	ASB6	NM_001202403.2		c.1099_1101delGTCinsCTT	p.Val367Leu	missense	N/A	NP_001189332.1	F6TX30
	ASB6	NM_177999.3		c.*483_*485delGTCinsCTT		3_prime_UTR	Exon 5 of 5	NP_821066.1	Q9NWX5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB6	ENST00000277458.5	TSL:1 MANE Select	c.1186_1188delGTCinsCTT	p.Val396Leu	missense	N/A	ENSP00000277458.4	Q9NWX5-1
	ASB6	ENST00000450050.6	TSL:1	c.1099_1101delGTCinsCTT	p.Val367Leu	missense	N/A	ENSP00000416172.3	F6TX30
	ASB6	ENST00000277459.8	TSL:1	c.*483_*485delGTCinsCTT		3_prime_UTR	Exon 5 of 5	ENSP00000277459.4	Q9NWX5-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.4

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: chr9-132400147;