dbSNP rs3738037: SRP9:c.72+89C>A (chr1-225778101-C-A) – 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.72+89C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,435,386 control chromosomes in the GnomAD database, including 17,988 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 0.22 ( 6207 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11781 hom. )

Consequence

SRP9
NM_003133.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.572

Publications

8 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:

Genome browser will be placed here

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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003133.6. 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
	SRP9	NM_003133.6	MANE Select	c.72+89C>A		intron	N/A	NP_003124.1	P49458-1
	SRP9	NM_001130440.2		c.72+89C>A		intron	N/A	NP_001123912.1	P49458-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRP9	ENST00000304786.12	TSL:1 MANE Select	c.72+89C>A	intron	N/A	ENSP00000305230.7	P49458-1
SRP9	ENST00000366839.8	TSL:1	c.72+89C>A	intron	N/A	ENSP00000355804.4	P49458-2
SRP9	ENST00000924809.1		c.72+89C>A	intron	N/A	ENSP00000594868.1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33409

AN:

152050

Hom.:

6197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.0821

Gnomad EAS

AF:

0.0721

Gnomad SAS

AF:

0.0631

Gnomad FIN

AF:

0.0886

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.190

GnomAD4 exome

AF:

0.115

AC:

148206

AN:

1283218

Hom.:

11781

AF XY:

0.112

AC XY:

72279

AN XY:

642896

show subpopulations

African (AFR)

AF:

0.532

AC:

15571

AN:

29254

American (AMR)

AF:

0.135

AC:

4973

AN:

36832

Ashkenazi Jewish (ASJ)

AF:

0.0766

AC:

1815

AN:

23702

East Asian (EAS)

AF:

0.104

AC:

3843

AN:

36902

South Asian (SAS)

AF:

0.0620

AC:

4893

AN:

78886

European-Finnish (FIN)

AF:

0.0921

AC:

4699

AN:

51028

Middle Eastern (MID)

AF:

0.120

AC:

645

AN:

5390

European-Non Finnish (NFE)

AF:

0.109

AC:

104962

AN:

967000

Other (OTH)

AF:

0.125

AC:

6805

AN:

54224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6179

12359

18538

24718

30897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3786

7572

11358

15144

18930

<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:

0.220

AC:

33449

AN:

152168

Hom.:

6207

Cov.:

AF XY:

0.214

AC XY:

15934

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.511

AC:

21202

AN:

41480

American (AMR)

AF:

0.159

AC:

2433

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0821

AC:

285

AN:

3470

East Asian (EAS)

AF:

0.0724

AC:

375

AN:

5178

South Asian (SAS)

AF:

0.0636

AC:

307

AN:

4826

European-Finnish (FIN)

AF:

0.0886

AC:

940

AN:

10610

Middle Eastern (MID)

AF:

0.147

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.108

AC:

7375

AN:

67986

Other (OTH)

AF:

0.189

AC:

400

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1095

2191

3286

4382

5477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.153

Hom.:

7803

Bravo

AF:

0.239

Asia WGS

AF:

0.0970

AC:

337

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.9

(source)

DANN

Benign

0.64

PhyloP100

-0.57

PromoterAI

-0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over