chr1-24654884-G-A

Variant names:

• chr1-24654884-G-A
• rs758508859
• NM_005839.4:c.1070G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005839.4(SRRM1):​c.1070G>A​(p.Gly357Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G357A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRRM1 NM_005839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90
• Publications: 0 publications found

Genes affected

SRRM1 (HGNC:16638): (serine and arginine repetitive matrix 1) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nuclear speck. Part of catalytic step 2 spliceosome. Biomarker of gestational diabetes. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37353313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005839.4. 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
	SRRM1	NM_005839.4	MANE Select	c.1070G>A	p.Gly357Glu	missense	Exon 9 of 17	NP_005830.2
	SRRM1	NM_001366595.1		c.1070G>A	p.Gly357Glu	missense	Exon 9 of 18	NP_001353524.1	A0A0S2Z4Z6
	SRRM1	NM_001366569.1		c.1070G>A	p.Gly357Glu	missense	Exon 9 of 18	NP_001353498.1	A0A994J7V4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM1	ENST00000323848.14	TSL:1 MANE Select	c.1070G>A	p.Gly357Glu	missense	Exon 9 of 17	ENSP00000326261.8	Q8IYB3-1
	SRRM1	ENST00000596378.1	TSL:1	c.953G>A	p.Gly318Glu	missense	Exon 9 of 15	ENSP00000471084.1	M0R088
	SRRM1	ENST00000928582.1		c.1124G>A	p.Gly375Glu	missense	Exon 10 of 19	ENSP00000598641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.28		Gain of solvent accessibility (P = 0.024)
MVP		0.32
MPC		0.48
ClinPred		0.87	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.20
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs758508859; hg19: chr1-24981375;