12-120462471-C-T

Variant names:

• chr12-120462471-C-T
• rs9040
• NM_176818.3:c.*2512C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	NM_176818.3	MANE Select	c.*2512C>T		3_prime_UTR	Exon 4 of 4	NP_789788.1	O43716
	SRSF9	NM_003769.3	MANE Select	c.523-309G>A		intron	N/A	NP_003760.1	Q13242
	GATC	NR_033684.2		n.3058C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	ENST00000551765.6	TSL:1 MANE Select	c.*2512C>T		3_prime_UTR	Exon 4 of 4	ENSP00000446872.1	O43716
	SRSF9	ENST00000229390.8	TSL:1 MANE Select	c.523-309G>A		intron	N/A	ENSP00000229390.3	Q13242
	SRSF9	ENST00000957766.1		c.523-309G>A		intron	N/A	ENSP00000627825.1

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

African (AFR) AF: 0.112 AC: 169 AN: 1506

American (AMR) AF: 0.293 AC: 763 AN: 2604

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 386 AN: 1964

East Asian (EAS) AF: 0.494 AC: 1399 AN: 2834

South Asian (SAS) AF: 0.283 AC: 2313 AN: 8172

European-Finnish (FIN) AF: 0.310 AC: 884 AN: 2854

Middle Eastern (MID) AF: 0.274 AC: 62 AN: 226

European-Non Finnish (NFE) AF: 0.305 AC: 11165 AN: 36592

Other (OTH) AF: 0.280 AC: 937 AN: 3344

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

African (AFR) AF: 0.109 AC: 4515 AN: 41488

American (AMR) AF: 0.273 AC: 4173 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2571 AN: 5172

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4822

European-Finnish (FIN) AF: 0.333 AC: 3517 AN: 10548

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21541 AN: 67958

Other (OTH) AF: 0.245 AC: 516 AN: 2106

Alfa AF: 0.272 Hom.: 1325

Bravo AF: 0.248

Asia WGS AF: 0.349 AC: 1215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9040; hg19: chr12-120900274;