chr1-2193702-G-T

Variant names:

• chr1-2193702-G-T
• rs746832136
• NM_182533.4:c.407C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182533.4(FAAP20):​c.407C>A​(p.Pro136Gln) 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. 13/19 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. P136L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAAP20 NM_182533.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

Genes affected

FAAP20 (HGNC:26428): (FA core complex associated protein 20) Enables K63-linked polyubiquitin modification-dependent protein binding activity and ubiquitin-dependent protein binding activity. Involved in interstrand cross-link repair and translesion synthesis. Located in cell junction; chromosome; and nuclear body. Part of Fanconi anaemia nuclear complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084391534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAAP20	NM_182533.4	c.407C>A	p.Pro136Gln	missense_variant	Exon 3 of 4	ENST00000378546.9	NP_872339.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAAP20	ENST00000378546.9	c.407C>A	p.Pro136Gln	missense_variant	Exon 3 of 4	1	NM_182533.4	ENSP00000367808.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.033	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L;L
PROVEAN	Uncertain	-3.1	D;N
REVEL	Benign	0.063
Sift	Benign	0.060	T;T
Sift4G	Uncertain	0.025	D;D
Polyphen		0.79	.;P
Vest4		0.18
MutPred		0.11		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.19
MPC		0.89
ClinPred		0.40	T
GERP RS		-2.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.085

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

Publications

LitVar

Other links and lift over

dbSNP: rs746832136; hg19: chr1-2125141;