Genetic Variant GATC:c.*3504C>T (chr12-120463463-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_176818.3(GATC):c.*3504C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,158 control chromosomes in the GnomAD database, including 3,788 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 0.18 ( 3787 hom., cov: 31)

Exomes 𝑓: 0.11 ( 1 hom. )

Consequence

GATC
NM_176818.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0520

Publications

10 publications found

Variant links:

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]

GATC links:

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]

SRSF9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GATC	NM_176818.3 link	c.*3504C>T	3_prime_UTR_variant	Exon 4 of 4	ENST00000551765.6	NP_789788.1
SRSF9	NM_003769.3 link	c.522+487G>A	intron_variant	Intron 3 of 3	ENST00000229390.8	NP_003760.1
GATC	NR_033684.2 link	n.4050C>T	non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATC	ENST00000551765.6 link	c.*3504C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_176818.3	ENSP00000446872.1
SRSF9	ENST00000229390.8 link	c.522+487G>A		intron_variant	Intron 3 of 3	1	NM_003769.3	ENSP00000229390.3

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27982

AN:

151890

Hom.:

3761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.0681

Gnomad SAS

AF:

0.0768

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.107

AC:

AN:

150

Hom.:

Cov.:

AF XY:

0.0875

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0789

AC:

AN:

114

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.185

AC:

28054

AN:

152008

Hom.:

3787

Cov.:

AF XY:

0.182

AC XY:

13542

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.384

AC:

15871

AN:

41384

American (AMR)

AF:

0.132

AC:

2016

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0562

AC:

195

AN:

3468

East Asian (EAS)

AF:

0.0682

AC:

353

AN:

5174

South Asian (SAS)

AF:

0.0769

AC:

371

AN:

4824

European-Finnish (FIN)

AF:

0.131

AC:

1389

AN:

10566

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7483

AN:

67990

Other (OTH)

AF:

0.141

AC:

297

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1054

2109

3163

4218

5272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.128

Hom.:

2163

Bravo

AF:

0.191

Asia WGS

AF:

0.116

AC:

404

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.8

(source)

DANN

Benign

0.55

PhyloP100

0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over