Genetic Variant SRP9:c.142-2411A>G (chr1-225786829-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003133.6(SRP9):c.142-2411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,247,838 control chromosomes in the GnomAD database, including 223,003 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 0.56 ( 24223 hom., cov: 28)

Exomes 𝑓: 0.60 ( 198780 hom. )

Consequence

SRP9
NM_003133.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

16 publications found

Variant links:

Genes affected

SRP9 (HGNC:11304): (signal recognition particle 9) Predicted to enable RNA binding activity and signal recognition particle binding activity. Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane. Predicted to be located in cytosol. Predicted to be part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

SRP9 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=-1.04).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP9	NM_003133.6 link	c.142-2411A>G		intron_variant	Intron 2 of 2	ENST00000304786.12	NP_003124.1	P49458-1
SRP9	NM_001130440.2 link	c.142-33A>G		intron_variant	Intron 2 of 3		NP_001123912.1	P49458-2A0A024R3P3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRP9	ENST00000304786.12 link	c.142-2411A>G		intron_variant	Intron 2 of 2	1	NM_003133.6	ENSP00000305230.7		P49458-1

Frequencies

GnomAD3 genomes

AF:

0.560

AC:

84201

AN:

150314

Hom.:

24203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.712

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.815

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.552

GnomAD2 exomes

AF:

0.628

AC:

73615

AN:

117218

AF XY:

0.631

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.685

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.819

Gnomad FIN exome

AF:

0.555

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.595

GnomAD4 exome

AF:

0.597

AC:

655676

AN:

1097428

Hom.:

198780

Cov.:

AF XY:

0.602

AC XY:

324457

AN XY:

539216

show subpopulations

African (AFR)

AF:

0.417

AC:

9302

AN:

22326

American (AMR)

AF:

0.686

AC:

16833

AN:

24550

Ashkenazi Jewish (ASJ)

AF:

0.529

AC:

8064

AN:

15250

East Asian (EAS)

AF:

0.808

AC:

10169

AN:

12592

South Asian (SAS)

AF:

0.701

AC:

50946

AN:

72640

European-Finnish (FIN)

AF:

0.549

AC:

7046

AN:

12824

Middle Eastern (MID)

AF:

0.503

AC:

1324

AN:

2630

European-Non Finnish (NFE)

AF:

0.590

AC:

528405

AN:

894930

Other (OTH)

AF:

0.594

AC:

23587

AN:

39686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10629

21258

31888

42517

53146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16754

33508

50262

67016

83770

<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:

0.560

AC:

84254

AN:

150410

Hom.:

24223

Cov.:

AF XY:

0.565

AC XY:

41441

AN XY:

73364

show subpopulations

African (AFR)

AF:

0.440

AC:

17978

AN:

40870

American (AMR)

AF:

0.621

AC:

9397

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1789

AN:

3460

East Asian (EAS)

AF:

0.815

AC:

4184

AN:

5136

South Asian (SAS)

AF:

0.714

AC:

3426

AN:

4796

European-Finnish (FIN)

AF:

0.569

AC:

5727

AN:

10066

Middle Eastern (MID)

AF:

0.503

AC:

146

AN:

290

European-Non Finnish (NFE)

AF:

0.588

AC:

39803

AN:

67680

Other (OTH)

AF:

0.557

AC:

1160

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1836

3671

5507

7342

9178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.575

Hom.:

45578

Bravo

AF:

0.557

Asia WGS

AF:

0.749

AC:

2604

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.4

(source)

DANN

Benign

0.56

PhyloP100

-2.0

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