NM_182533.4:c.213C>T

Variant names:

• chr1-2193896-G-A
• NM_182533.4:c.213C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_182533.4(FAAP20):​c.213C>T​(p.Gly71Gly) 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182533.4. 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
	FAAP20	NM_182533.4	MANE Select	c.213C>T	p.Gly71Gly	synonymous	Exon 3 of 4	NP_872339.3	Q6NZ36-1
	FAAP20	NM_001146310.2		c.200C>T	p.Ala67Val	missense	Exon 7 of 8	NP_001139782.1	Q6ZRT9
	FAAP20	NM_001256945.2		c.77C>T	p.Ala26Val	missense	Exon 2 of 3	NP_001243874.2	F6S8H2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAP20	ENST00000378546.9	TSL:1 MANE Select	c.213C>T	p.Gly71Gly	synonymous	Exon 3 of 4	ENSP00000367808.4	Q6NZ36-1
	FAAP20	ENST00000420515.1	TSL:1	c.210C>T	p.Gly70Gly	synonymous	Exon 3 of 4	ENSP00000409721.1	H7C361
	FAAP20	ENST00000401813.7	TSL:1	n.2052C>T		non_coding_transcript_exon	Exon 3 of 4

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

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111720

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

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	0.23
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
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.073
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.038
Sift4G	Benign	0.079	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
Mutation Taster		=296/4	polymorphism

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

Other links and lift over

hg19: chr1-2125335;