X-14865121-CAT-TAG

Variant names:

• chrX-14865121-CAT-TAG
• NM_001018113.3:c.388_390delATGinsCTA
• FANCB p.Met130Leu

Variant summary

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

The NM_001018113.3(FANCB):​c.388_390delATGinsCTA​(p.Met130Leu) 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. M130V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FANCB NM_001018113.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.96
• Publications: 0 publications found

Genes affected

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

FANCB Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group B

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• VACTERL association, X-linked, with or without hydrocephalus

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• VACTERL with hydrocephalus

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018113.3. 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
	FANCB	NM_001018113.3	MANE Select	c.388_390delATGinsCTA	p.Met130Leu	missense	N/A	NP_001018123.1	Q8NB91
	FANCB	NM_001410764.1		c.388_390delATGinsCTA	p.Met130Leu	missense	N/A	NP_001397693.1	A0A8Q3WL66
	FANCB	NM_001324162.2		c.388_390delATGinsCTA	p.Met130Leu	missense	N/A	NP_001311091.1	Q8NB91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	ENST00000650831.1	MANE Select	c.388_390delATGinsCTA	p.Met130Leu	missense	N/A	ENSP00000498215.1	Q8NB91
	FANCB	ENST00000324138.7	TSL:1	c.388_390delATGinsCTA	p.Met130Leu	missense	N/A	ENSP00000326819.3	Q8NB91
	FANCB	ENST00000452869.2	TSL:1	c.388_390delATGinsCTA	p.Met130Leu	missense	N/A	ENSP00000397849.2	C9J5X9

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0

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: chrX-14883243;