rs142959373

chrX-14845014-A-CchrX-14845014-A-GchrX-14845014-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001018113.3(FANCB):c.1769T>G(p.Phe590Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F590S) 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: 5.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCB	NM_001018113.3	c.1769T>G	p.Phe590Cys	missense_variant	8/10	ENST00000650831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCB	ENST00000650831.1	c.1769T>G	p.Phe590Cys	missense_variant	8/10		NM_001018113.3	P2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D;D;T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.69	T;.;T
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.52
MutPred		0.60		Loss of stability (P = 0.0629);Loss of stability (P = 0.0629);Loss of stability (P = 0.0629);
MVP		0.46
MPC		0.59
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs142959373; hg19: chrX-14863136;