1-2193896-G-A

Position:

• chr1-2193896-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_182533.4(FAAP20):​c.213C>T​(p.Gly71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAAP20 NM_182533.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0730

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0790835).
• BP7: Synonymous conserved (PhyloP=0.073 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAP20	NM_182533.4	c.213C>T	p.Gly71=	synonymous_variant	3/4	ENST00000378546.9	NP_872339.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAP20	ENST00000378546.9	c.213C>T	p.Gly71=	synonymous_variant	3/4	1	NM_182533.4	ENSP00000367808	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459898 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726292

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

The c.200C>T (p.A67V) alteration is located in exon 7 (coding exon 3) of the FAAP20 gene. This alteration results from a C to T substitution at nucleotide position 200, causing the alanine (A) at amino acid position 67 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.1
DANN	Benign	0.76
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PROVEAN	Benign	-2.0	.;N
REVEL	Benign	0.038
Sift4G	Benign	0.079	T;T
Vest4		0.16
MVP		0.34
ClinPred		0.067	T
GERP RS		-3.3
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
gMVP		0.013

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-2125335;