rs576290614

Variant names:

• chr1-29148894-C-A
• NM_005626.5:c.1001G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-29148894-C-A
• chr1-29148894-C-G
• chr1-29148894-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005626.5(SRSF4):​c.1001G>T​(p.Ser334Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S334T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SRSF4 NM_005626.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22536355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF4	NM_005626.5	c.1001G>T	p.Ser334Ile	missense_variant	Exon 6 of 6	ENST00000373795.7	NP_005617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRSF4	ENST00000373795.7	c.1001G>T	p.Ser334Ile	missense_variant	Exon 6 of 6	1	NM_005626.5	ENSP00000362900.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459234 Hom.: 0 Cov.: 111 AF XY: 0.00000275 AC XY: 2 AN XY: 725958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;.
Vest4		0.31
MutPred		0.40		Loss of phosphorylation at S334 (P = 0);.;
MVP		0.20
MPC		0.27
ClinPred		0.88	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-29475406;