12-120459849-T-C

Variant names:

• chr12-120459849-T-C
• rs28390349
• NM_176818.3:c.359-58T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_176818.3(GATC):​c.359-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 1,384,158 control chromosomes in the GnomAD database, including 322,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41803 hom., cov: 32)
  • Exomes 𝑓: 0.67 (280663 hom.)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.37
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 12-120459849-T-C is Benign according to our data. Variant chr12-120459849-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 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.359-58T>C		intron	N/A	NP_789788.1	O43716
	GATC	NR_033684.2		n.494-58T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	ENST00000551765.6	TSL:1 MANE Select	c.359-58T>C		intron	N/A	ENSP00000446872.1	O43716
	ENSG00000111780	ENST00000551806.1	TSL:3	c.452-58T>C		intron	N/A	ENSP00000450281.1	H0YIV9
	SRSF9	ENST00000957766.1		c.*5+2165A>G		intron	N/A	ENSP00000627825.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 111041 AN: 152008 Hom.: 41741 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.667

GnomAD4 exome AF: 0.673 AC: 828718 AN: 1232032 Hom.: 280663 AF XY: 0.673 AC XY: 418358 AN XY: 622024

African (AFR) AF: 0.923 AC: 26197 AN: 28370

American (AMR) AF: 0.568 AC: 23917 AN: 42106

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 17189 AN: 23746

East Asian (EAS) AF: 0.705 AC: 25765 AN: 36528

South Asian (SAS) AF: 0.680 AC: 54322 AN: 79858

European-Finnish (FIN) AF: 0.689 AC: 34292 AN: 49736

Middle Eastern (MID) AF: 0.659 AC: 2734 AN: 4150

European-Non Finnish (NFE) AF: 0.665 AC: 609283 AN: 916050

Other (OTH) AF: 0.680 AC: 35019 AN: 51488

GnomAD4 genome AF: 0.731 AC: 111161 AN: 152126 Hom.: 41803 Cov.: 32 AF XY: 0.731 AC XY: 54324 AN XY: 74354

African (AFR) AF: 0.916 AC: 38034 AN: 41540

American (AMR) AF: 0.611 AC: 9329 AN: 15278

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

East Asian (EAS) AF: 0.725 AC: 3752 AN: 5176

South Asian (SAS) AF: 0.681 AC: 3281 AN: 4816

European-Finnish (FIN) AF: 0.689 AC: 7275 AN: 10562

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

European-Non Finnish (NFE) AF: 0.660 AC: 44835 AN: 67968

Other (OTH) AF: 0.661 AC: 1394 AN: 2108

Alfa AF: 0.701 Hom.: 4459

Bravo AF: 0.730

Asia WGS AF: 0.708 AC: 2466 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.51
PhyloP100		-3.4
Mutation Taster		=10/90	disease causing

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: rs28390349; hg19: chr12-120897652;