2-38750470-A-T

Variant names:

• chr2-38750470-A-T
• rs3134628
• NM_001031684.3:c.29-276T>A

Variant summary

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

The NM_001031684.3(SRSF7):​c.29-276T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,304 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 0.0000066 (0 hom., cov: 27)
• Consequence: SRSF7 NM_001031684.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 3 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.29-276T>A		intron	N/A	NP_001026854.1	Q16629-1
	SRSF7	NM_001363802.1		c.29-276T>A		intron	N/A	NP_001350731.1	C9JAB2
	SRSF7	NM_001195446.2		c.29-276T>A		intron	N/A	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.29-276T>A		intron	N/A	ENSP00000325905.6	Q16629-1
	SRSF7	ENST00000926871.1		c.29-276T>A		intron	N/A	ENSP00000596930.1
	SRSF7	ENST00000409276.5	TSL:5	c.29-276T>A		intron	N/A	ENSP00000386806.1	C9JAB2

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151304 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

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

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

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151304 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 73824

African (AFR) AF: 0.00 AC: 0 AN: 41192

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5062

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67816

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 39402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.58
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.47		Position offset: 3

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

Other links and lift over

dbSNP: rs3134628; hg19: chr2-38977612;