chr19-12924703-C-T

Variant names:

• chr19-12924703-C-T
• rs113870503
• NM_004461.3:c.1131G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004461.3(FARSA):​c.1131G>A​(p.Val377Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,594,498 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (3 hom.)
• Consequence: FARSA NM_004461.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.49
• Publications: 0 publications found

Genes affected

FARSA (HGNC:3592): (phenylalanyl-tRNA synthetase subunit alpha) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. This gene encodes a product which is similar to the catalytic subunit of prokaryotic and Saccharomyces cerevisiae phenylalanyl-tRNA synthetases (PheRS). This gene product has been shown to be expressed in a tumor-selective and cell cycle stage- and differentiation-dependent manner, the first member of the tRNA synthetase gene family shown to exhibit this type of regulated expression [provided by RefSeq, Jul 2008]

FARSA Gene-Disease associations (from GenCC):

• Rajab interstitial lung disease with brain calcifications 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-12924703-C-T is Benign according to our data. Variant chr19-12924703-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3056955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.49 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004461.3. 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
	FARSA	NM_004461.3	MANE Select	c.1131G>A	p.Val377Val	synonymous	Exon 10 of 13	NP_004452.1	Q9Y285-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARSA	ENST00000314606.9	TSL:1 MANE Select	c.1131G>A	p.Val377Val	synonymous	Exon 10 of 13	ENSP00000320309.3	Q9Y285-1
	FARSA	ENST00000588025.5	TSL:5	c.1251G>A	p.Val417Val	synonymous	Exon 11 of 14	ENSP00000468051.1	K7ER00
	FARSA	ENST00000941155.1		c.1065G>A	p.Val355Val	synonymous	Exon 10 of 13	ENSP00000611214.1

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 554 AN: 152228 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000936 AC: 224 AN: 239292 AF XY: 0.000700

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.000445

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.000688

GnomAD4 exome AF: 0.000418 AC: 603 AN: 1442152 Hom.: 3 Cov.: 34 AF XY: 0.000367 AC XY: 262 AN XY: 714350

African (AFR) AF: 0.0134 AC: 446 AN: 33226

American (AMR) AF: 0.000731 AC: 32 AN: 43800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39400

South Asian (SAS) AF: 0.00 AC: 0 AN: 83670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52738

Middle Eastern (MID) AF: 0.000879 AC: 5 AN: 5690

European-Non Finnish (NFE) AF: 0.0000246 AC: 27 AN: 1099382

Other (OTH) AF: 0.00156 AC: 93 AN: 59464

GnomAD4 genome AF: 0.00364 AC: 554 AN: 152346 Hom.: 4 Cov.: 32 AF XY: 0.00370 AC XY: 276 AN XY: 74498

African (AFR) AF: 0.0126 AC: 524 AN: 41588

American (AMR) AF: 0.00150 AC: 23 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00235 Hom.: 0

Bravo AF: 0.00436

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	FARSA-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.3
DANN	Benign	0.75
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs113870503; hg19: chr19-13035517; COSMIC: COSV58904613; COSMIC: COSV58904613;