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GeneBe

20-43460026-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006275.6(SRSF6):c.382-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00927 in 1,614,104 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 8 hom., cov: 33)
Exomes 𝑓: 0.0095 ( 112 hom. )

Consequence

SRSF6
NM_006275.6 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00001162
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.301
Variant links:
Genes affected
SRSF6 (HGNC:10788): (serine and arginine rich splicing factor 6) The protein encoded by this gene is involved in mRNA splicing and may play a role in the determination of alternative splicing. The encoded nuclear protein belongs to the splicing factor SR family and has been shown to bind with and modulate another member of the family, SFRS12. Alternative splicing results in multiple transcript variants. In addition, two pseudogenes, one on chromosome 17 and the other on the X chromosome, have been found for this gene.[provided by RefSeq, Sep 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 20-43460026-C-T is Benign according to our data. Variant chr20-43460026-C-T is described in ClinVar as [Benign]. Clinvar id is 779389.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00698 (1063/152268) while in subpopulation SAS AF= 0.0222 (107/4828). AF 95% confidence interval is 0.0188. There are 8 homozygotes in gnomad4. There are 519 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1063 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRSF6NM_006275.6 linkuse as main transcriptc.382-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000244020.5
SRSF6NR_034009.2 linkuse as main transcriptn.788-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRSF6ENST00000244020.5 linkuse as main transcriptc.382-7C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_006275.6 P2Q13247-1

Frequencies

GnomAD3 genomes
AF:
0.00699
AC:
1063
AN:
152150
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00157
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0115
Gnomad ASJ
AF:
0.0167
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0221
Gnomad FIN
AF:
0.00170
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.00894
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00933
AC:
2344
AN:
251310
Hom.:
30
AF XY:
0.0106
AC XY:
1445
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.00142
Gnomad AMR exome
AF:
0.00741
Gnomad ASJ exome
AF:
0.0147
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0251
Gnomad FIN exome
AF:
0.00189
Gnomad NFE exome
AF:
0.00899
Gnomad OTH exome
AF:
0.0137
GnomAD4 exome
AF:
0.00951
AC:
13900
AN:
1461836
Hom.:
112
Cov.:
32
AF XY:
0.0102
AC XY:
7442
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00119
Gnomad4 AMR exome
AF:
0.00861
Gnomad4 ASJ exome
AF:
0.0155
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0255
Gnomad4 FIN exome
AF:
0.00210
Gnomad4 NFE exome
AF:
0.00894
Gnomad4 OTH exome
AF:
0.0108
GnomAD4 genome
AF:
0.00698
AC:
1063
AN:
152268
Hom.:
8
Cov.:
33
AF XY:
0.00697
AC XY:
519
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00156
Gnomad4 AMR
AF:
0.0115
Gnomad4 ASJ
AF:
0.0167
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0222
Gnomad4 FIN
AF:
0.00170
Gnomad4 NFE
AF:
0.00894
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00808
Hom.:
6
Bravo
AF:
0.00755
Asia WGS
AF:
0.00722
AC:
25
AN:
3478
EpiCase
AF:
0.0124
EpiControl
AF:
0.0129

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.41
DANN
Benign
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000012
dbscSNV1_RF
Benign
0.046
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: rs80163090; hg19: chr20-42088666; API