12-120459756-C-T

Variant names:

• chr12-120459756-C-T
• rs35801170
• NM_176818.3:c.359-151C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_176818.3(GATC):​c.359-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 463,626 control chromosomes in the GnomAD database, including 112,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (41716 hom., cov: 32)
  • Exomes 𝑓: 0.67 (71125 hom.)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.88
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 12-120459756-C-T is Benign according to our data. Variant chr12-120459756-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182274.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.359-151C>T		intron	N/A	NP_789788.1	O43716
	GATC	NR_033684.2		n.494-151C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATC	ENST00000551765.6	TSL:1 MANE Select	c.359-151C>T		intron	N/A	ENSP00000446872.1	O43716
	ENSG00000111780	ENST00000551806.1	TSL:3	c.452-151C>T		intron	N/A	ENSP00000450281.1	H0YIV9
	SRSF9	ENST00000957766.1		c.*5+2258G>A		intron	N/A	ENSP00000627825.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110968 AN: 152026 Hom.: 41659 Cov.: 32

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.672 AC: 209248 AN: 311482 Hom.: 71125 AF XY: 0.673 AC XY: 113402 AN XY: 168442

African (AFR) AF: 0.909 AC: 6435 AN: 7078

American (AMR) AF: 0.584 AC: 7100 AN: 12158

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 5889 AN: 8292

East Asian (EAS) AF: 0.703 AC: 11873 AN: 16894

South Asian (SAS) AF: 0.685 AC: 28050 AN: 40972

European-Finnish (FIN) AF: 0.691 AC: 20951 AN: 30324

Middle Eastern (MID) AF: 0.648 AC: 773 AN: 1192

European-Non Finnish (NFE) AF: 0.658 AC: 117598 AN: 178786

Other (OTH) AF: 0.670 AC: 10579 AN: 15786

GnomAD4 genome AF: 0.730 AC: 111083 AN: 152144 Hom.: 41716 Cov.: 32 AF XY: 0.730 AC XY: 54284 AN XY: 74352

African (AFR) AF: 0.913 AC: 37956 AN: 41562

American (AMR) AF: 0.610 AC: 9325 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2509 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3754 AN: 5166

South Asian (SAS) AF: 0.680 AC: 3281 AN: 4822

European-Finnish (FIN) AF: 0.689 AC: 7279 AN: 10564

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

European-Non Finnish (NFE) AF: 0.660 AC: 44839 AN: 67964

Other (OTH) AF: 0.658 AC: 1389 AN: 2110

Alfa AF: 0.707 Hom.: 4786

Bravo AF: 0.729

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.78
DANN	Benign	0.92
PhyloP100		-1.9
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: rs35801170; hg19: chr12-120897559;