chr17-81545810-C-G

Variant names:

• chr17-81545810-C-G
• rs777046070
• NM_025161.6:c.2246G>C

Variant summary

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

The NM_025161.6(FAAP100):​c.2246G>C​(p.Arg749Pro) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R749Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAAP100 NM_025161.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.769
• Publications: 0 publications found

Genes affected

FAAP100 (HGNC:26171): (FA core complex associated protein 100) FAAP100 is a component of the Fanconi anemia (FA; MIM 277650) core complex and is required for core complex stability and FANCD2 (see MIM 227646) monoubiquitination (Ling et al., 2007 [PubMed 17396147]).[supplied by OMIM, Mar 2008]

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=0.11154127).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025161.6. 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
	FAAP100	NM_025161.6	MANE Select	c.2246G>C	p.Arg749Pro	missense	Exon 6 of 9	NP_079437.5
	FAAP100	NR_033338.2		n.2465G>C		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAP100	ENST00000327787.13	TSL:1 MANE Select	c.2246G>C	p.Arg749Pro	missense	Exon 6 of 9	ENSP00000333283.8	Q0VG06-1
	FAAP100	ENST00000425898.2	TSL:1	c.1193G>C	p.Arg398Pro	missense	Exon 2 of 5	ENSP00000399674.2	E7EVV8
	FAAP100	ENST00000443656.6	TSL:1	n.*2148G>C		non_coding_transcript_exon	Exon 6 of 9	ENSP00000395348.2	J3KQD8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.0
DANN	Benign	0.94
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.77
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.14
Sift	Benign	0.24	T
Sift4G	Uncertain	0.051	T
Polyphen		0.74	P
Vest4		0.20
MutPred		0.42		Loss of helix (P = 0.0072)
MVP		0.17
MPC		0.52
ClinPred		0.13	T
GERP RS		-3.9
Varity_R		0.13
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs777046070; hg19: chr17-79512836;