chr12-120459969-T-G

Variant names:

• chr12-120459969-T-G
• rs115350072
• NM_176818.3:c.*10T>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_176818.3(GATC):​c.*10T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,606,764 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (133 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (89 hom.)
• Consequence: GATC NM_176818.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.119
• Publications: 1 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 12-120459969-T-G is Benign according to our data. Variant chr12-120459969-T-G is described in ClinVar as Benign. ClinVar VariationId is 1236331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0762 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.*10T>G		3_prime_UTR	Exon 4 of 4	NP_789788.1	O43716
	GATC	NR_033684.2		n.556T>G		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.*10T>G		3_prime_UTR	Exon 4 of 4	ENSP00000446872.1	O43716
	ENSG00000111780	ENST00000551806.1	TSL:3	c.*10T>G		3_prime_UTR	Exon 5 of 5	ENSP00000450281.1	H0YIV9
	GATC	ENST00000920762.1		c.*10T>G		3_prime_UTR	Exon 4 of 4	ENSP00000590821.1

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3455 AN: 152214 Hom.: 133 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0162

GnomAD2 exomes AF: 0.00552 AC: 1383 AN: 250608 AF XY: 0.00388

Gnomad AFR exome AF: 0.0756

Gnomad AMR exome AF: 0.00319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00214 AC: 3114 AN: 1454432 Hom.: 89 Cov.: 27 AF XY: 0.00185 AC XY: 1340 AN XY: 723944

African (AFR) AF: 0.0764 AC: 2539 AN: 33228

American (AMR) AF: 0.00361 AC: 161 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5754

European-Non Finnish (NFE) AF: 0.000106 AC: 117 AN: 1105774

Other (OTH) AF: 0.00454 AC: 273 AN: 60076

GnomAD4 genome AF: 0.0227 AC: 3453 AN: 152332 Hom.: 133 Cov.: 32 AF XY: 0.0214 AC XY: 1597 AN XY: 74500

African (AFR) AF: 0.0784 AC: 3258 AN: 41552

American (AMR) AF: 0.00941 AC: 144 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68034

Other (OTH) AF: 0.0161 AC: 34 AN: 2116

Alfa AF: 0.0149 Hom.: 35

Bravo AF: 0.0260

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

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	-0.40
CADD	Benign	6.8
DANN	Benign	0.86
PhyloP100		0.12
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: rs115350072; hg19: chr12-120897772;