rs35902209

Variant names:

• chr11-3038163-C-G
• NM_001014437.3:c.688G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-3038163-C-G
• chr11-3038163-C-T

Variant summary

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

The NM_001014437.3(CARS1):​c.688G>C​(p.Asp230His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 4.42

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]

CARS1-AS1 (HGNC:40125): (CARS1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.688G>C	p.Asp230His	missense_variant	Exon 7 of 23	ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.688G>C	p.Asp230His	missense_variant	Exon 7 of 23	1	NM_001014437.3	ENSP00000369897.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 31 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	.;D;.;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.9	.;M;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.9	D;D;D;.
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D;D;D;.
Sift4G	Uncertain	0.042	D;D;D;D
Polyphen		1.0, 0.91	.;D;D;P
Vest4		0.53
MutPred		0.51		.;Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);.;
MVP		0.63
MPC		0.93
ClinPred		0.99	D
GERP RS		1.8
Varity_R		0.74
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-3059393;