chr12-120462471-C-T

Position:

• chr12-120462471-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176818.3(GATC):​c.*2512C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 212,140 control chromosomes in the GnomAD database, including 8,886 homozygotes. 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: 𝑓 0.26 (5927 hom., cov: 32)
  • Exomes 𝑓: 0.30 (2959 hom.)
• Consequence: GATC NM_176818.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

Genes affected

GATC (HGNC:25068): (glutamyl-tRNA amidotransferase subunit C) Enables glutaminyl-tRNA synthase (glutamine-hydrolyzing) activity. Involved in glutaminyl-tRNAGln biosynthesis via transamidation and mitochondrial translation. Located in mitochondrion. Part of glutamyl-tRNA(Gln) amidotransferase complex. Implicated in combined oxidative phosphorylation deficiency 42. [provided by Alliance of Genome Resources, Apr 2022]

SRSF9 (HGNC:10791): (serine and arginine rich splicing factor 9) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two pseudogenes, one on chromosome 15 and the other on chromosome 21, have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATC	NM_176818.3	c.*2512C>T		3_prime_UTR_variant	4/4	ENST00000551765.6
SRSF9	NM_003769.3	c.523-309G>A		intron_variant		ENST00000229390.8
GATC	NR_033684.2	n.3058C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATC	ENST00000551765.6	c.*2512C>T		3_prime_UTR_variant	4/4	1	NM_176818.3	P1
SRSF9	ENST00000229390.8	c.523-309G>A		intron_variant		1	NM_003769.3	P3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39258 AN: 151926 Hom.: 5915 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.301 AC: 18078 AN: 60096 Hom.: 2959 Cov.: 2 AF XY: 0.303 AC XY: 9876 AN XY: 32592

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.293

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.258 AC: 39282 AN: 152044 Hom.: 5927 Cov.: 32 AF XY: 0.262 AC XY: 19452 AN XY: 74294

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.245

Alfa AF: 0.276 Hom.: 1320

Bravo AF: 0.248

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9040; hg19: chr12-120900274;