chr1-24652438-A-T

Variant names:

• chr1-24652438-A-T
• rs377349401
• NM_005839.4:c.730A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005839.4(SRRM1):​c.730A>T​(p.Ile244Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000646 in 1,549,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: SRRM1 NM_005839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1570428).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

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.730A>T	p.Ile244Phe	missense	Exon 7 of 17	NP_005830.2
	SRRM1	NM_001366595.1		c.730A>T	p.Ile244Phe	missense	Exon 7 of 18	NP_001353524.1	A0A0S2Z4Z6
	SRRM1	NM_001366569.1		c.730A>T	p.Ile244Phe	missense	Exon 7 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.730A>T	p.Ile244Phe	missense	Exon 7 of 17	ENSP00000326261.8	Q8IYB3-1
	SRRM1	ENST00000596378.1	TSL:1	c.613A>T	p.Ile205Phe	missense	Exon 7 of 15	ENSP00000471084.1	M0R088
	SRRM1	ENST00000928582.1		c.730A>T	p.Ile244Phe	missense	Exon 7 of 19	ENSP00000598641.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151858 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000967 AC: 2 AN: 206722 AF XY: 0.00000883

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000644 AC: 9 AN: 1397184 Hom.: 0 Cov.: 31 AF XY: 0.00000721 AC XY: 5 AN XY: 693604

African (AFR) AF: 0.00 AC: 0 AN: 29774

American (AMR) AF: 0.00 AC: 0 AN: 31148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23590

East Asian (EAS) AF: 0.00 AC: 0 AN: 38284

South Asian (SAS) AF: 0.000119 AC: 9 AN: 75464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085624

Other (OTH) AF: 0.00 AC: 0 AN: 57280

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151966 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2106

ExAC AF: 0.00000824 AC: 1

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	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.7
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.082
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.27	T
Polyphen		0.40	B
Vest4		0.48
MutPred		0.21		Gain of phosphorylation at T241 (P = 0.0853)
MVP		0.093
MPC		0.58
ClinPred		0.39	T
GERP RS		6.0
Varity_R		0.39
gMVP		0.30
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs377349401; hg19: chr1-24978929;