rs771998496

chrX-14864959-C-AchrX-14864959-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L184L) 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: 0.0760

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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/exons	MANE	UniProt
FANCB	NM_001018113.3	c.552G>T	p.Leu184Phe	missense_variant	3/10	ENST00000650831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCB	ENST00000650831.1	c.552G>T	p.Leu184Phe	missense_variant	3/10		NM_001018113.3	P2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

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;.
MutationTaster	Benign	0.94	D;D
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs771998496; hg19: chrX-14883081;