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GeneBe

9-136377606-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003086.4(SNAPC4):c.4221T>C(p.Ser1407=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,543,320 control chromosomes in the GnomAD database, including 132,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11391 hom., cov: 34)
Exomes 𝑓: 0.41 ( 120706 hom. )

Consequence

SNAPC4
NM_003086.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.265
Variant links:
Genes affected
SNAPC4 (HGNC:11137): (small nuclear RNA activating complex polypeptide 4) This gene encodes the largest subunit of the small nuclear RNA-activating protein (SNAP) complex. The encoded protein contains a Myb DNA-binding domain, and is essential for RNA polymerase II and III polymerase transcription from small nuclear RNA promoters. A mutation in this gene is associated with ankylosing spondylitis. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-136377606-A-G is Benign according to our data. Variant chr9-136377606-A-G is described in ClinVar as [Benign]. Clinvar id is 402489.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.265 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNAPC4NM_003086.4 linkuse as main transcriptc.4221T>C p.Ser1407= synonymous_variant 22/24 ENST00000684778.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNAPC4ENST00000684778.1 linkuse as main transcriptc.4221T>C p.Ser1407= synonymous_variant 22/24 NM_003086.4 P1
SNAPC4ENST00000298532.2 linkuse as main transcriptc.4221T>C p.Ser1407= synonymous_variant 21/231 P1
SNAPC4ENST00000637388.2 linkuse as main transcriptc.4221T>C p.Ser1407= synonymous_variant 22/245 P1
SNAPC4ENST00000689006.1 linkuse as main transcriptc.*3434T>C 3_prime_UTR_variant, NMD_transcript_variant 22/24

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.380
AC:
57786
AN:
151968
Hom.:
11373
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.293
Gnomad AMI
AF:
0.414
Gnomad AMR
AF:
0.472
Gnomad ASJ
AF:
0.355
Gnomad EAS
AF:
0.311
Gnomad SAS
AF:
0.330
Gnomad FIN
AF:
0.414
Gnomad MID
AF:
0.199
Gnomad NFE
AF:
0.419
Gnomad OTH
AF:
0.354
GnomAD3 exomes
AF:
0.404
AC:
82573
AN:
204442
Hom.:
17316
AF XY:
0.398
AC XY:
43903
AN XY:
110382
show subpopulations
Gnomad AFR exome
AF:
0.289
Gnomad AMR exome
AF:
0.537
Gnomad ASJ exome
AF:
0.356
Gnomad EAS exome
AF:
0.298
Gnomad SAS exome
AF:
0.329
Gnomad FIN exome
AF:
0.414
Gnomad NFE exome
AF:
0.423
Gnomad OTH exome
AF:
0.413
GnomAD4 exome
AF:
0.413
AC:
574608
AN:
1391234
Hom.:
120706
Cov.:
45
AF XY:
0.410
AC XY:
280112
AN XY:
683956
show subpopulations
Gnomad4 AFR exome
AF:
0.284
Gnomad4 AMR exome
AF:
0.536
Gnomad4 ASJ exome
AF:
0.352
Gnomad4 EAS exome
AF:
0.318
Gnomad4 SAS exome
AF:
0.321
Gnomad4 FIN exome
AF:
0.416
Gnomad4 NFE exome
AF:
0.426
Gnomad4 OTH exome
AF:
0.394
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.380
AC:
57855
AN:
152086
Hom.:
11391
Cov.:
34
AF XY:
0.379
AC XY:
28172
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.294
Gnomad4 AMR
AF:
0.473
Gnomad4 ASJ
AF:
0.355
Gnomad4 EAS
AF:
0.310
Gnomad4 SAS
AF:
0.330
Gnomad4 FIN
AF:
0.414
Gnomad4 NFE
AF:
0.419
Gnomad4 OTH
AF:
0.356
Alfa
AF:
0.411
Hom.:
9758
Bravo
AF:
0.378
Asia WGS
AF:
0.387
AC:
1346
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
Cadd
Benign
0.30
Dann
Benign
0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10781507; hg19: chr9-139272058; COSMIC: COSV53733284; COSMIC: COSV53733284; API