NM_176818.3:c.255-194C>T

Variant names:

• chr12-120456882-C-T
• rs7137953
• NM_176818.3:c.255-194C>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.255-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,142 control chromosomes in the GnomAD database, including 3,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3470 hom., cov: 32)
• Consequence: GATC NM_176818.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.270
• Publications: 17 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=-0.69).
• BP6: Variant 12-120456882-C-T is Benign according to our data. Variant chr12-120456882-C-T is described in ClinVar as Benign. ClinVar VariationId is 1263252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 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.255-194C>T		intron	N/A	NP_789788.1	O43716
	GATC	NR_033684.2		n.390-194C>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.255-194C>T		intron	N/A	ENSP00000446872.1	O43716
	ENSG00000111780	ENST00000551806.1	TSL:3	c.348-194C>T		intron	N/A	ENSP00000450281.1	H0YIV9
	SRSF9	ENST00000957766.1		c.*6-513G>A		intron	N/A	ENSP00000627825.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30831 AN: 152024 Hom.: 3471 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.203 AC: 30840 AN: 152142 Hom.: 3470 Cov.: 32 AF XY: 0.200 AC XY: 14914 AN XY: 74388

African (AFR) AF: 0.281 AC: 11647 AN: 41474

American (AMR) AF: 0.154 AC: 2348 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1309 AN: 3472

East Asian (EAS) AF: 0.157 AC: 813 AN: 5194

South Asian (SAS) AF: 0.204 AC: 984 AN: 4816

European-Finnish (FIN) AF: 0.128 AC: 1361 AN: 10604

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11640 AN: 67982

Other (OTH) AF: 0.203 AC: 427 AN: 2108

Alfa AF: 0.186 Hom.: 1876

Bravo AF: 0.209

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

ClinVar submissions

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	-0.69
CADD	Benign	5.4
DANN	Benign	0.85
PhyloP100		-0.27
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: rs7137953; hg19: chr12-120894685;