chr6-36594664-C-G

Variant names:

• chr6-36594664-C-G
• rs1406945
• NM_003017.5:c.-3+183C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003017.5(SRSF3):​c.-3+183C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,062 control chromosomes in the GnomAD database, including 14,193 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 0.41 (14189 hom., cov: 32)
  • Exomes 𝑓: 0.33 (4 hom.)
• Consequence: SRSF3 NM_003017.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 5 publications found

Genes affected

SRSF3 (HGNC:10785): (serine and arginine rich splicing factor 3) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants, one protein-coding and the other non-coding, have been found for this gene. [provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003017.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF3	NM_003017.5	MANE Select	c.-3+183C>G		intron	N/A	NP_003008.1
	SRSF3	NR_036610.2		n.120+183C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF3	ENST00000373715.11	TSL:1 MANE Select	c.-3+183C>G		intron	N/A	ENSP00000362820.5
	SRSF3	ENST00000620941.2	TSL:3	c.-94C>G		5_prime_UTR	Exon 1 of 6	ENSP00000482833.1
	SRSF3	ENST00000855355.1		c.-3+282C>G		intron	N/A	ENSP00000525414.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62273 AN: 151862 Hom.: 14144 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.384

GnomAD4 exome AF: 0.329 AC: 27 AN: 82 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 20 AN XY: 60

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.319 AC: 23 AN: 72

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.410 AC: 62383 AN: 151980 Hom.: 14189 Cov.: 32 AF XY: 0.416 AC XY: 30872 AN XY: 74264

African (AFR) AF: 0.586 AC: 24306 AN: 41444

American (AMR) AF: 0.441 AC: 6741 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3074 AN: 5160

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4812

European-Finnish (FIN) AF: 0.404 AC: 4255 AN: 10544

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20018 AN: 67960

Other (OTH) AF: 0.385 AC: 813 AN: 2110

Alfa AF: 0.193 Hom.: 396

Bravo AF: 0.428

Asia WGS AF: 0.451 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-1.4
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1406945; hg19: chr6-36562441;