chr1-24652591-C-T

Variant names:

• chr1-24652591-C-T
• rs903935382
• NM_005839.4:c.883C>T

Variant summary

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

The NM_005839.4(SRRM1):​c.883C>T​(p.His295Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,470 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SRRM1 NM_005839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.91

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRRM1	NM_005839.4	c.883C>T	p.His295Tyr	missense_variant	Exon 7 of 17	ENST00000323848.14	NP_005830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRRM1	ENST00000323848.14	c.883C>T	p.His295Tyr	missense_variant	Exon 7 of 17	1	NM_005839.4	ENSP00000326261.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460470 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726572

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.883C>T (p.H295Y) alteration is located in exon 7 (coding exon 7) of the SRRM1 gene. This alteration results from a C to T substitution at nucleotide position 883, causing the histidine (H) at amino acid position 295 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T;T;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;T;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.7	N;N;N;.
REVEL	Benign	0.21
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Benign	0.083	T;T;T;T
Polyphen		0.98	D;.;D;.
Vest4		0.52
MutPred		0.22		Gain of phosphorylation at H295 (P = 0.0081);Gain of phosphorylation at H295 (P = 0.0081);Gain of phosphorylation at H295 (P = 0.0081);.;
MVP		0.42
MPC		0.42
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.20
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs903935382; hg19: chr1-24979082;