12-120463463-C-T

Position:

• chr12-120463463-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.*3504C>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 0.184 in 152,158 control chromosomes in the GnomAD database, including 3,788 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 0.18 (3787 hom., cov: 31)
  • Exomes 𝑓: 0.11 (1 hom.)
• Consequence: GATC NM_176818.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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]

GATC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATC	NM_176818.3	c.*3504C>T		3_prime_UTR_variant	4/4	ENST00000551765.6	NP_789788.1
SRSF9	NM_003769.3	c.522+487G>A		intron_variant		ENST00000229390.8	NP_003760.1
GATC	NR_033684.2	n.4050C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATC	ENST00000551765.6	c.*3504C>T		3_prime_UTR_variant	4/4	1	NM_176818.3	ENSP00000446872.1
SRSF9	ENST00000229390.8	c.522+487G>A		intron_variant		1	NM_003769.3	ENSP00000229390.3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27982 AN: 151890 Hom.: 3761 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.107 AC: 16 AN: 150 Hom.: 1 Cov.: 0 AF XY: 0.0875 AC XY: 7 AN XY: 80

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0789

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.185 AC: 28054 AN: 152008 Hom.: 3787 Cov.: 31 AF XY: 0.182 AC XY: 13542 AN XY: 74302

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.141

Alfa AF: 0.116 Hom.: 1285

Bravo AF: 0.191

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.55

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: rs7027; hg19: chr12-120901266;