NM_001320214.2:c.*786A>C

Variant names:

• chr14-69772247-A-C
• rs6573908
• NM_001320214.2:c.*786A>C

Variant summary

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

The NM_001320214.2(SRSF5):​c.*786A>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,076 control chromosomes in the GnomAD database, including 12,208 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 0.37 (12208 hom., cov: 33)
• Consequence: SRSF5 NM_001320214.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 4 publications found

Genes affected

SRSF5 (HGNC:10787): (serine and arginine rich splicing factor 5) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF5	NM_001320214.2	c.*786A>C		downstream_gene_variant		ENST00000557154.6	NP_001307143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF5	ENST00000557154.6	c.*786A>C		downstream_gene_variant		2	NM_001320214.2	ENSP00000451088.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55636 AN: 151960 Hom.: 12156 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 55755 AN: 152076 Hom.: 12208 Cov.: 33 AF XY: 0.363 AC XY: 26978 AN XY: 74344

African (AFR) AF: 0.608 AC: 25200 AN: 41452

American (AMR) AF: 0.399 AC: 6095 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3464

East Asian (EAS) AF: 0.165 AC: 854 AN: 5178

South Asian (SAS) AF: 0.194 AC: 939 AN: 4828

European-Finnish (FIN) AF: 0.268 AC: 2841 AN: 10588

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18215 AN: 67976

Other (OTH) AF: 0.357 AC: 753 AN: 2110

Alfa AF: 0.280 Hom.: 10318

Bravo AF: 0.384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.085
DANN	Benign	0.61
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6573908; hg19: chr14-70238964;