chr1-24650061-A-G

Variant names:

• chr1-24650061-A-G
• NM_005839.4:c.496A>G

Variant summary

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

The NM_005839.4(SRRM1):​c.496A>G​(p.Arg166Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SRRM1 NM_005839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.11
• 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=0.27075255).

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.496A>G	p.Arg166Gly	missense	Exon 5 of 17	NP_005830.2
	SRRM1	NM_001366595.1		c.496A>G	p.Arg166Gly	missense	Exon 5 of 18	NP_001353524.1	A0A0S2Z4Z6
	SRRM1	NM_001366569.1		c.496A>G	p.Arg166Gly	missense	Exon 5 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.496A>G	p.Arg166Gly	missense	Exon 5 of 17	ENSP00000326261.8	Q8IYB3-1
	SRRM1	ENST00000596378.1	TSL:1	c.379A>G	p.Arg127Gly	missense	Exon 5 of 15	ENSP00000471084.1	M0R088
	SRRM1	ENST00000928582.1		c.496A>G	p.Arg166Gly	missense	Exon 5 of 19	ENSP00000598641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1438076 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 713060

African (AFR) AF: 0.00 AC: 0 AN: 32856

American (AMR) AF: 0.00 AC: 0 AN: 41166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25600

East Asian (EAS) AF: 0.00 AC: 0 AN: 39208

South Asian (SAS) AF: 0.00 AC: 0 AN: 82160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099764

Other (OTH) AF: 0.00 AC: 0 AN: 59560

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	Pathogenic	0.60
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.15
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.027	D
Polyphen		0.42	B
Vest4		0.42
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.23
MPC		0.47
ClinPred		0.88	D
GERP RS		5.3
Varity_R		0.55
gMVP		0.45
Mutation Taster		=49/51	disease causing

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: chr1-24976552; COSMIC: COSV60477242; COSMIC: COSV60477242;