rs771998496

Variant names:

• chrX-14864959-C-A
• rs771998496
• NM_001018113.3:c.552G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-14864959-C-A
• chrX-14864959-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001018113.3(FANCB):​c.552G>T​(p.Leu184Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L184L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: FANCB NM_001018113.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0760
• 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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1684818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3	c.552G>T	p.Leu184Phe	missense_variant	Exon 3 of 10	ENST00000650831.1	NP_001018123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1	c.552G>T	p.Leu184Phe	missense_variant	Exon 3 of 10		NM_001018113.3	ENSP00000498215.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia complementation group B Uncertain:1

Jan 14, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.66	T;.;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M;M;.
PhyloP100		0.076
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.77	P;P;.
Vest4		0.31
MutPred		0.24		Gain of ubiquitination at K187 (P = 0.0898);Gain of ubiquitination at K187 (P = 0.0898);Gain of ubiquitination at K187 (P = 0.0898);
MVP		0.20
MPC		0.38
ClinPred		0.80	D
GERP RS		0.89
Varity_R		0.12
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs771998496; hg19: chrX-14883081;