NM_001031684.3:c.368G>A

Variant names:

• chr2-38749547-C-T
• NM_001031684.3:c.368G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031684.3(SRSF7):​c.368G>A​(p.Ser123Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRSF7 NM_001031684.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87
• Publications: 0 publications found

Genes affected

SRSF7 (HGNC:10789): (serine and arginine rich splicing factor 7) 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 N-terminal RNA recognition motif (RRM) for binding RNA and a C-terminal 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2420741).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031684.3. 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
	SRSF7	NM_001031684.3	MANE Select	c.368G>A	p.Ser123Asn	missense	Exon 3 of 8	NP_001026854.1	Q16629-1
	SRSF7	NM_001363802.1		c.368G>A	p.Ser123Asn	missense	Exon 3 of 8	NP_001350731.1	C9JAB2
	SRSF7	NM_001195446.2		c.368G>A	p.Ser123Asn	missense	Exon 3 of 7	NP_001182375.1	Q16629-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF7	ENST00000313117.11	TSL:1 MANE Select	c.368G>A	p.Ser123Asn	missense	Exon 3 of 8	ENSP00000325905.6	Q16629-1
	SRSF7	ENST00000926871.1		c.368G>A	p.Ser123Asn	missense	Exon 3 of 8	ENSP00000596930.1
	SRSF7	ENST00000409276.5	TSL:5	c.368G>A	p.Ser123Asn	missense	Exon 3 of 8	ENSP00000386806.1	C9JAB2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.46
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.54	N
REVEL	Uncertain	0.32
Sift	Benign	0.46	T
Sift4G	Benign	0.097	T
Polyphen		0.98	D
Vest4		0.27
MutPred		0.28		Loss of phosphorylation at S123 (P = 5e-04)
MVP		0.59
MPC		1.6
ClinPred		0.82	D
GERP RS		6.0
PromoterAI		0.015	Neutral
Varity_R		0.22
gMVP		0.71
Mutation Taster		=50/50

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

hg19: chr2-38976689;