12-120457486-C-G

Variant names:

• chr12-120457486-C-G
• rs3847971
• NM_176818.3:c.358+307C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176818.3(GATC):​c.358+307C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,900 control chromosomes in the GnomAD database, including 41,679 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 0.73 (41679 hom., cov: 30)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 10 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]

ENSG00000111780 (HGNC:):

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 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.358+307C>G		intron	N/A	NP_789788.1	O43716
	GATC	NR_033684.2		n.493+307C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	ENST00000551765.6	TSL:1 MANE Select	c.358+307C>G		intron	N/A	ENSP00000446872.1	O43716
	ENSG00000111780	ENST00000551806.1	TSL:3	c.451+307C>G		intron	N/A	ENSP00000450281.1	H0YIV9
	SRSF9	ENST00000957766.1		c.*6-1117G>C		intron	N/A	ENSP00000627825.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110821 AN: 151780 Hom.: 41622 Cov.: 30

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.665

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.730 AC: 110937 AN: 151900 Hom.: 41679 Cov.: 30 AF XY: 0.730 AC XY: 54216 AN XY: 74218

African (AFR) AF: 0.914 AC: 37902 AN: 41464

American (AMR) AF: 0.611 AC: 9307 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3757 AN: 5168

South Asian (SAS) AF: 0.679 AC: 3259 AN: 4798

European-Finnish (FIN) AF: 0.689 AC: 7243 AN: 10506

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44825 AN: 67948

Other (OTH) AF: 0.659 AC: 1388 AN: 2106

Alfa AF: 0.589 Hom.: 1586

Bravo AF: 0.729

Asia WGS AF: 0.709 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.81
PhyloP100		-2.3
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: rs3847971; hg19: chr12-120895289;