NM_006275.6:c.382-7C>T

Variant names:

• chr20-43460026-C-T
• rs80163090
• NM_006275.6:c.382-7C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Publications: 2 publications found

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]

ENSG00000288000 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1063 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006275.6. 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
	SRSF6	NM_006275.6	MANE Select	c.382-7C>T		splice_region intron	N/A	NP_006266.2
	SRSF6	NR_034009.2		n.788-7C>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF6	ENST00000244020.5	TSL:1 MANE Select	c.382-7C>T		splice_region intron	N/A	ENSP00000244020.3	Q13247-1
	ENSG00000288000	ENST00000657241.1		c.361-7C>T		splice_region intron	N/A	ENSP00000499734.1	A0A590UK80
	SRSF6	ENST00000945325.1		c.379-7C>T		splice_region intron	N/A	ENSP00000615384.1

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 1063 AN: 152150 Hom.: 8 Cov.: 33

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

GnomAD2 exomes AF: 0.00933 AC: 2344 AN: 251310 AF XY: 0.0106

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 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

African (AFR) AF: 0.00119 AC: 40 AN: 33478

American (AMR) AF: 0.00861 AC: 385 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 404 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0255 AC: 2195 AN: 86242

European-Finnish (FIN) AF: 0.00210 AC: 112 AN: 53410

Middle Eastern (MID) AF: 0.0279 AC: 161 AN: 5768

European-Non Finnish (NFE) AF: 0.00894 AC: 9946 AN: 1111992

Other (OTH) AF: 0.0108 AC: 652 AN: 60394

GnomAD4 genome AF: 0.00698 AC: 1063 AN: 152268 Hom.: 8 Cov.: 33 AF XY: 0.00697 AC XY: 519 AN XY: 74452

African (AFR) AF: 0.00156 AC: 65 AN: 41554

American (AMR) AF: 0.0115 AC: 176 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4828

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10602

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00894 AC: 608 AN: 68022

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.44
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs80163090; hg19: chr20-42088666;