dbSNP rs17290456: SRP19:c.301+542T>C (chr5-112865274-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003135.3(SRP19):c.301+542T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 152,414 control chromosomes in the GnomAD database, including 218 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 0.042 ( 218 hom., cov: 32)

Exomes 𝑓: 0.040 ( 0 hom. )

Consequence

SRP19
NM_003135.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.26

Publications

1 publications found

Variant links:

Genes affected

SRP19 (HGNC:11300): (signal recognition particle 19) Enables 7S RNA binding activity. Contributes to ribosome binding activity. Predicted to be involved in SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition. Located in nucleolus. Part of signal recognition particle, endoplasmic reticulum targeting. [provided by Alliance of Genome Resources, Apr 2022]

SRP19 Gene-Disease associations (from GenCC):

neutropenia
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

SRP19 links:

ENSG00000258864 (HGNC:):

ENSG00000258864 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRP19	NM_003135.3	MANE Select	c.301+542T>C	intron	N/A	NP_003126.1	P09132-1
SRP19	NM_001204194.2		c.229+542T>C	intron	N/A	NP_001191123.1	A0A087WYR0
SRP19	NM_001204193.2		c.301+542T>C	intron	N/A	NP_001191122.1	P09132-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRP19	ENST00000505459.6	TSL:1 MANE Select	c.301+542T>C	intron	N/A	ENSP00000424870.1	P09132-1
SRP19	ENST00000282999.7	TSL:1	c.301+542T>C	intron	N/A	ENSP00000282999.3	P09132-2
ENSG00000258864	ENST00000520401.1	TSL:3	n.*231+542T>C	intron	N/A	ENSP00000454861.1	H3BNH8

Frequencies

GnomAD3 genomes

AF:

0.0423

AC:

6434

AN:

152170

Hom.:

218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0479

Gnomad ASJ

AF:

0.0913

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00871

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0669

Gnomad OTH

AF:

0.0499

GnomAD4 exome

AF:

0.0403

AC:

AN:

124

Hom.:

AF XY:

0.0323

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0385

AC:

AN:

104

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0422

AC:

6434

AN:

152290

Hom.:

218

Cov.:

AF XY:

0.0388

AC XY:

2887

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0123

AC:

510

AN:

41558

American (AMR)

AF:

0.0478

AC:

731

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0913

AC:

317

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.00934

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0129

AC:

137

AN:

10614

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0669

AC:

4548

AN:

68030

Other (OTH)

AF:

0.0493

AC:

104

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

320

639

959

1278

1598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0565

Hom.:

202

Bravo

AF:

0.0448

Asia WGS

AF:

0.00924

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

2.3

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over