chr17-76737069-C-T

Variant names:

• chr17-76737069-C-T
• NM_001195427.2:c.92G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001195427.2(SRSF2):​c.92G>A​(p.Arg31Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SRSF2 NM_001195427.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 2 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.7085 (below the threshold of 3.09). Trascript score misZ: 3.8222 (above the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195427.2. 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
	SRSF2	NM_001195427.2	MANE Select	c.92G>A	p.Arg31Lys	missense	Exon 1 of 3	NP_001182356.1	Q01130-1
	SRSF2	NM_003016.5		c.92G>A	p.Arg31Lys	missense	Exon 1 of 2	NP_003007.2
	MFSD11	NM_001242534.3		c.-94C>T		5_prime_UTR	Exon 1 of 14	NP_001229463.1	O43934-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF2	ENST00000359995.10	TSL:1 MANE Select	c.92G>A	p.Arg31Lys	missense	Exon 1 of 3	ENSP00000353089.5	Q01130-1
	SRSF2	ENST00000392485.2	TSL:1	c.92G>A	p.Arg31Lys	missense	Exon 1 of 2	ENSP00000376276.2	Q01130-1
	MFSD11	ENST00000621483.4	TSL:1	c.-94C>T		5_prime_UTR	Exon 1 of 14	ENSP00000485005.1	O43934-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.048
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.78	N
PhyloP100		5.8
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Benign	0.17	T
Sift4G	Benign	0.60	T
Polyphen		0.092	B
Vest4		0.61
MutPred		0.52		Gain of methylation at R31 (P = 0.0151)
MVP		0.70
MPC		1.8
ClinPred		0.89	D
GERP RS		4.0
PromoterAI		0.037	Neutral
Varity_R		0.67
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr17-74733151;