rs150231327

Variant names:

• chr15-89291661-T-A
• rs150231327
• NM_001113378.2:c.1939T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-89291661-T-A
• chr15-89291661-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001113378.2(FANCI):​c.1939T>A​(p.Leu647Ile) 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. 14/22 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. L647L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FANCI NM_001113378.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

Genes affected

FANCI (HGNC:25568): (FA complementation group I) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group I. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FANCI Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group I

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34292507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCI	NM_001113378.2	c.1939T>A	p.Leu647Ile	missense_variant	Exon 20 of 38	ENST00000310775.12	NP_001106849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCI	ENST00000310775.12	c.1939T>A	p.Leu647Ile	missense_variant	Exon 20 of 38	1	NM_001113378.2	ENSP00000310842.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia complementation group I Uncertain:1

Aug 09, 2023

Baylor 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	0.10
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	.;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M
PhyloP100		1.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.93	P;P
Vest4		0.31
MutPred		0.58		Gain of catalytic residue at L652 (P = 0.0216);Gain of catalytic residue at L652 (P = 0.0216);
MVP		0.64
MPC		0.047
ClinPred		0.91	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.36
Mutation Taster		=85/15	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: rs150231327; hg19: chr15-89834892;