Variant 20-43460026-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006275.6(SRSF6):c.382-7C>T variant causes a splice region, 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, intron

Scores

Splicing: ADA: 0.00001162

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

SRSF6 links:

ENSG00000288000 (HGNC:):

ENSG00000288000 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
SRSF6	NM_006275.6 linkuse as main transcript	c.382-7C>T		splice_region_variant, intron_variant		ENST00000244020.5	NP_006266.2	Q13247-1
SRSF6	NR_034009.2 linkuse as main transcript	n.788-7C>T		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRSF6	ENST00000244020.5 linkuse as main transcript	c.382-7C>T		splice_region_variant, intron_variant		1	NM_006275.6	ENSP00000244020.3		Q13247-1
ENSG00000288000	ENST00000657241.1 linkuse as main transcript	c.361-7C>T		splice_region_variant, intron_variant				ENSP00000499734.1		A0A590UK80

Frequencies

GnomAD3 genomes

AF:

0.00699

AC:

1063

AN:

152150

Hom.:

Cov.:

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.:

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.:

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.:

Cov.:

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.:

Bravo

AF:

0.00755

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0124

EpiControl

AF:

0.0129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over