chr14-73279390-AG-TA

Variant names:

• chr14-73279390-AG-TA
• NM_001005743.2:c.1130_1131delCTinsTA
• NUMB p.Ala377Val

Variant summary

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

The NM_001005743.2(NUMB):​c.1130_1131delCTinsTA​(p.Ala377Val) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A377D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NUMB NM_001005743.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.40
• Publications: 0 publications found

Genes affected

NUMB (HGNC:8060): (NUMB endocytic adaptor protein) The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005743.2. 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
	NUMB	NM_001005743.2	MANE Select	c.1130_1131delCTinsTA	p.Ala377Val	missense	N/A	NP_001005743.1	P49757-1
	NUMB	NM_003744.6		c.1097_1098delCTinsTA	p.Ala366Val	missense	N/A	NP_003735.3
	NUMB	NM_001005744.2		c.1097-2098_1097-2097delCTinsTA		intron	N/A	NP_001005744.1	P49757-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUMB	ENST00000555238.6	TSL:1 MANE Select	c.1130_1131delCTinsTA	p.Ala377Val	missense	N/A	ENSP00000451300.1	P49757-1
	NUMB	ENST00000557597.5	TSL:1	c.1097_1098delCTinsTA	p.Ala366Val	missense	N/A	ENSP00000451117.1	P49757-3
	NUMB	ENST00000556772.5	TSL:1	c.698_699delCTinsTA	p.Ala233Val	missense	N/A	ENSP00000451513.1	G3V3Z8

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.4

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: chr14-73746098;