NM_005687.5:c.1595G>C

Variant names:

• chr2-222599951-C-G
• rs1016325037
• NM_005687.5:c.1595G>C

Variant summary

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

The NM_005687.5(FARSB):​c.1595G>C​(p.Gly532Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000375 in 1,601,232 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FARSB NM_005687.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33
• 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.1595G>C	p.Gly532Ala	missense	Exon 16 of 17	NP_005678.3
	FARSB	NR_130154.2		n.1810G>C		non_coding_transcript_exon	Exon 17 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARSB	ENST00000281828.8	TSL:1 MANE Select	c.1595G>C	p.Gly532Ala	missense	Exon 16 of 17	ENSP00000281828.6	Q9NSD9-1
	FARSB	ENST00000875114.1		c.1709G>C	p.Gly570Ala	missense	Exon 17 of 18	ENSP00000545173.1
	FARSB	ENST00000875112.1		c.1706G>C	p.Gly569Ala	missense	Exon 17 of 18	ENSP00000545171.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449126 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720968

African (AFR) AF: 0.0000924 AC: 3 AN: 32480

American (AMR) AF: 0.00 AC: 0 AN: 40432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 39168

South Asian (SAS) AF: 0.00 AC: 0 AN: 83676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108742

Other (OTH) AF: 0.00 AC: 0 AN: 59908

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152106 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74310

African (AFR) AF: 0.0000725 AC: 3 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.3
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.27
Sift	Uncertain	0.027	D
Sift4G	Benign	0.11	T
Polyphen		0.87	P
Vest4		0.42
MVP		0.60
MPC		0.25
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.61
gMVP		0.83
Mutation Taster		=8/92	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: rs1016325037; hg19: chr2-223464670;