17-76737321-G-C

Variant names:

• chr17-76737321-G-C
• rs3744061
• NM_001195427.2:c.-161C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001195427.2(SRSF2):​c.-161C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000451 in 975,418 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00020 (0 hom., cov: 35)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SRSF2 NM_001195427.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 32 publications found

Genes affected

SRSF2 (HGNC:10783): (serine and arginine rich splicing factor 2) 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 encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267168 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BS2: High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF2	NM_001195427.2	c.-161C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	ENST00000359995.10	NP_001182356.1
SRSF2	NM_001195427.2	c.-161C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000359995.10	NP_001182356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF2	ENST00000359995.10	c.-161C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5
SRSF2	ENST00000359995.10	c.-161C>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_001195427.2	ENSP00000353089.5
ENSG00000267168	ENST00000587459.1	c.239-961G>C		intron_variant	Intron 1 of 1	5		ENSP00000466829.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152096 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000170 AC: 14 AN: 823204 Hom.: 0 Cov.: 10 AF XY: 0.00000734 AC XY: 3 AN XY: 408738

African (AFR) AF: 0.000623 AC: 12 AN: 19276

American (AMR) AF: 0.00 AC: 0 AN: 18122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15268

East Asian (EAS) AF: 0.00 AC: 0 AN: 31470

South Asian (SAS) AF: 0.00 AC: 0 AN: 46690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2644

European-Non Finnish (NFE) AF: 0.00000321 AC: 2 AN: 623014

Other (OTH) AF: 0.00 AC: 0 AN: 37416

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152214 Hom.: 0 Cov.: 35 AF XY: 0.000202 AC XY: 15 AN XY: 74388

African (AFR) AF: 0.000698 AC: 29 AN: 41560

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 41904

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.61
DANN	Benign	0.72
PhyloP100		-1.3
PromoterAI		0.25	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1

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: rs3744061; hg19: chr17-74733403;