Genetic Variant NM_003133.6: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:

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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=-0.77).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRP9	NM_003133.6 link	c.72+89C>A		intron_variant	Intron 1 of 2	ENST00000304786.12	NP_003124.1	P49458-1
SRP9	NM_001130440.2 link	c.72+89C>A		intron_variant	Intron 1 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.72+89C>A		intron_variant	Intron 1 of 2	1	NM_003133.6	ENSP00000305230.7		P49458-1

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 v4.3

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

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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