1-29148528-G-A

Variant names:

• chr1-29148528-G-A
• NM_005626.5:c.1367C>T

Variant summary

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

The NM_005626.5(SRSF4):​c.1367C>T​(p.Ser456Leu) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRSF4 NM_005626.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.57
• Publications: 0 publications found

Genes affected

SRSF4 (HGNC:10786): (serine and arginine rich splicing factor 4) Enables RNA binding activity. Involved in negative regulation of mRNA splicing, via spliceosome. Located in nuclear speck. Biomarker of Down syndrome; acute myeloid leukemia; clear cell renal cell carcinoma; and colon adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000305828 (HGNC:):

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=0.14553893).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005626.5. 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
	SRSF4	NM_005626.5	MANE Select	c.1367C>T	p.Ser456Leu	missense	Exon 6 of 6	NP_005617.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF4	ENST00000373795.7	TSL:1 MANE Select	c.1367C>T	p.Ser456Leu	missense	Exon 6 of 6	ENSP00000362900.4	Q08170
	SRSF4	ENST00000870274.1		c.1385C>T	p.Ser462Leu	missense	Exon 6 of 6	ENSP00000540333.1
	SRSF4	ENST00000969505.1		c.1361C>T	p.Ser454Leu	missense	Exon 6 of 6	ENSP00000639564.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	Benign	0.10
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.6
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.14
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.061	B
Vest4		0.15
MutPred		0.39		Loss of phosphorylation at S456 (P = 3e-04)
MVP		0.23
MPC		0.20
ClinPred		0.82	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.39
Mutation Taster		=74/26	polymorphism

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: chr1-29475040;