chr2-222571977-C-A

Variant names:

• chr2-222571977-C-A
• rs774298156
• NM_005687.5:c.1664G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005687.5(FARSB):​c.1664G>T​(p.Gly555Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FARSB NM_005687.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72
• Publications: 0 publications found

Genes affected

FARSB (HGNC:17800): (phenylalanyl-tRNA synthetase subunit beta) This gene encodes a highly conserved enzyme that belongs to the aminoacyl-tRNA synthetase class IIc subfamily. This enzyme comprises the regulatory beta subunits that form a tetramer with two catalytic alpha subunits. In the presence of ATP, this tetramer is responsible for attaching L-phenylalanine to the terminal adenosine of the appropriate tRNA. A pseudogene located on chromosome 10 has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

FARSB Gene-Disease associations (from GenCC):

• Rajab interstitial lung disease with brain calcifications 1

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005687.5. 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
	FARSB	NM_005687.5	MANE Select	c.1664G>T	p.Gly555Val	missense	Exon 17 of 17	NP_005678.3
	FARSB	NR_130154.2		n.1879G>T		non_coding_transcript_exon	Exon 18 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARSB	ENST00000281828.8	TSL:1 MANE Select	c.1664G>T	p.Gly555Val	missense	Exon 17 of 17	ENSP00000281828.6	Q9NSD9-1
	FARSB	ENST00000875114.1		c.1778G>T	p.Gly593Val	missense	Exon 18 of 18	ENSP00000545173.1
	FARSB	ENST00000875112.1		c.1775G>T	p.Gly592Val	missense	Exon 18 of 18	ENSP00000545171.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.33	B
Vest4		0.55
MutPred		0.63		Loss of sheet (P = 0.0817)
MVP		0.27
MPC		0.42
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.72
gMVP		0.92
Mutation Taster		=28/72	disease causing

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: rs774298156; hg19: chr2-223436696;