chr17-81547182-C-G

Variant names:

• chr17-81547182-C-G
• rs1425005033
• NM_025161.6:c.1900G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025161.6(FAAP100):​c.1900G>C​(p.Glu634Gln) 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. 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. E634K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAAP100 NM_025161.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057041705).

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.1900G>C	p.Glu634Gln	missense	Exon 5 of 9	NP_079437.5
	FAAP100	NR_033338.2		n.2119G>C		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAP100	ENST00000327787.13	TSL:1 MANE Select	c.1900G>C	p.Glu634Gln	missense	Exon 5 of 9	ENSP00000333283.8	Q0VG06-1
	FAAP100	ENST00000425898.2	TSL:1	c.847G>C	p.Glu283Gln	missense	Exon 1 of 5	ENSP00000399674.2	E7EVV8
	FAAP100	ENST00000443656.6	TSL:1	n.*1802G>C		non_coding_transcript_exon	Exon 5 of 9	ENSP00000395348.2	J3KQD8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.8
DANN	Benign	0.94
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.25
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.023
Sift	Benign	0.27	T
Sift4G	Benign	0.19	T
Polyphen		0.59	P
Vest4		0.24
MutPred		0.095		Loss of catalytic residue at E634 (P = 0.0596)
MVP		0.18
MPC		0.44
ClinPred		0.21	T
GERP RS		1.6
Varity_R		0.036
gMVP		0.36

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: rs1425005033; hg19: chr17-79514208;