Genetic Variant NM_004596.5:c.600+97T>C (chr19-40763171-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_004596.5(SNRPA):c.600+97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 952,128 control chromosomes in the GnomAD database, including 54,310 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 0.27 ( 7111 hom., cov: 32)

Exomes 𝑓: 0.34 ( 47199 hom. )

Consequence

SNRPA
NM_004596.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.382

Publications

9 publications found

Variant links:

Genes affected

SNRPA (HGNC:11151): (small nuclear ribonucleoprotein polypeptide A) The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5' splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation. [provided by RefSeq, Oct 2010]

SNRPA Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SNRPA 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004596.5. 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
	SNRPA	NM_004596.5	MANE Select	c.600+97T>C		intron	N/A	NP_004587.1	P09012

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNRPA	ENST00000243563.8	TSL:1 MANE Select	c.600+97T>C	intron	N/A	ENSP00000243563.2	P09012
SNRPA	ENST00000925562.1		c.732+97T>C	intron	N/A	ENSP00000595621.1
SNRPA	ENST00000861888.1		c.693+97T>C	intron	N/A	ENSP00000531947.1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41465

AN:

151990

Hom.:

7105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0692

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.341

AC:

272758

AN:

800020

Hom.:

47199

Cov.:

AF XY:

0.340

AC XY:

137284

AN XY:

403412

show subpopulations

African (AFR)

AF:

0.0590

AC:

1091

AN:

18478

American (AMR)

AF:

0.458

AC:

8976

AN:

19588

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

3903

AN:

15592

East Asian (EAS)

AF:

0.429

AC:

13934

AN:

32464

South Asian (SAS)

AF:

0.326

AC:

17699

AN:

54228

European-Finnish (FIN)

AF:

0.347

AC:

14658

AN:

42250

Middle Eastern (MID)

AF:

0.246

AC:

943

AN:

3834

European-Non Finnish (NFE)

AF:

0.346

AC:

199449

AN:

576232

Other (OTH)

AF:

0.324

AC:

12105

AN:

37354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

9231

18463

27694

36926

46157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5166

10332

15498

20664

25830

<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:

0.273

AC:

41480

AN:

152108

Hom.:

7111

Cov.:

AF XY:

0.277

AC XY:

20575

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.0691

AC:

2869

AN:

41544

American (AMR)

AF:

0.408

AC:

6228

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

888

AN:

3468

East Asian (EAS)

AF:

0.436

AC:

2249

AN:

5162

South Asian (SAS)

AF:

0.335

AC:

1616

AN:

4822

European-Finnish (FIN)

AF:

0.346

AC:

3665

AN:

10584

Middle Eastern (MID)

AF:

0.257

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.337

AC:

22875

AN:

67948

Other (OTH)

AF:

0.292

AC:

617

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1455

2910

4365

5820

7275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.322

Hom.:

11578

Bravo

AF:

0.270

Asia WGS

AF:

0.403

AC:

1400

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.8

(source)

DANN

Benign

0.83

PhyloP100

-0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over