chr11-3017132-C-A

Variant names:

• chr11-3017132-C-A
• rs766200492
• NM_001014437.3:c.1891G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001014437.3(CARS1):​c.1891G>T​(p.Ala631Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CARS1 NM_001014437.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66

Genes affected

CARS1 (HGNC:1493): (cysteinyl-tRNA synthetase 1) This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25523576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.1891G>T	p.Ala631Ser	missense_variant	Exon 16 of 23	ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.1891G>T	p.Ala631Ser	missense_variant	Exon 16 of 23	1	NM_001014437.3	ENSP00000369897.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251182 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461720 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727152

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	.;T;.;.
Eigen	Benign	0.064
Eigen_PC	Benign	0.080
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	.;L;L;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.4	N;N;N;.
REVEL	Benign	0.075
Sift	Benign	0.067	T;T;T;.
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.57, 0.96, 0.67	.;P;D;P
Vest4		0.30
MutPred		0.46		.;Gain of MoRF binding (P = 0.1246);Gain of MoRF binding (P = 0.1246);.;
MVP		0.57
MPC		0.40
ClinPred		0.40	T
GERP RS		3.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.096
gMVP		0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs766200492; hg19: chr11-3038362;