NM_025161.6:c.1960C>G

Variant names:

• chr17-81547122-G-C
• rs774903762
• NM_025161.6:c.1960C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025161.6(FAAP100):​c.1960C>G​(p.Arg654Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000726 in 1,376,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R654H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FAAP100 NM_025161.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28
• Publications: 2 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

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.1960C>G	p.Arg654Gly	missense	Exon 5 of 9	NP_079437.5
	FAAP100	NR_033338.2		n.2179C>G		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.1960C>G	p.Arg654Gly	missense	Exon 5 of 9	ENSP00000333283.8	Q0VG06-1
	FAAP100	ENST00000425898.2	TSL:1	c.907C>G	p.Arg303Gly	missense	Exon 1 of 5	ENSP00000399674.2	E7EVV8
	FAAP100	ENST00000443656.6	TSL:1	n.*1862C>G		non_coding_transcript_exon	Exon 5 of 9	ENSP00000395348.2	J3KQD8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376482 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 675550

African (AFR) AF: 0.00 AC: 0 AN: 30778

American (AMR) AF: 0.00 AC: 0 AN: 32246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20464

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38920

South Asian (SAS) AF: 0.00 AC: 0 AN: 74236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069218

Other (OTH) AF: 0.00 AC: 0 AN: 56524

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.083	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.3
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0289)
MVP		0.72
MPC		1.3
ClinPred		0.97	D
GERP RS		4.9
Varity_R		0.65
gMVP		0.67

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: rs774903762; hg19: chr17-79514148;