NM_001014437.3:c.2241G>T

Variant names:

• chr11-3002577-C-A
• NM_001014437.3:c.2241G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001014437.3(CARS1):​c.2241G>T​(p.Lys747Asn) 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 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CARS1 NM_001014437.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26876143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.2241G>T	p.Lys747Asn	missense_variant	Exon 21 of 23	ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.2241G>T	p.Lys747Asn	missense_variant	Exon 21 of 23	1	NM_001014437.3	ENSP00000369897.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;.;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.090
FATHMM_MKL	Benign	0.74	D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Pathogenic	3.3	.;M;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N;N;N;.
REVEL	Benign	0.14
Sift	Uncertain	0.017	D;D;D;.
Sift4G	Uncertain	0.047	D;T;T;T
Polyphen		0.85, 0.60, 0.69	.;P;P;P
Vest4		0.38
MutPred		0.18		.;Loss of methylation at K664 (P = 0.0376);Loss of methylation at K664 (P = 0.0376);.;
MVP		0.60
MPC		0.37
ClinPred		0.93	D
GERP RS		3.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Varity_R		0.24
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-3023807;