7-76265386-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001110199.3(SRRM3):​c.748C>T​(p.Arg250Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,601,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SRRM3
NM_001110199.3 missense

Scores

2
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.925
Variant links:
Genes affected
SRRM3 (HGNC:26729): (serine/arginine repetitive matrix 3) Predicted to enable mRNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.075546116).
BS2
High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRRM3NM_001110199.3 linkc.748C>T p.Arg250Trp missense_variant Exon 10 of 15 ENST00000611745.2 NP_001103669.1 A0A087WXA3
SRRM3NM_001291831.2 linkc.748C>T p.Arg250Trp missense_variant Exon 10 of 16 NP_001278760.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRRM3ENST00000611745.2 linkc.748C>T p.Arg250Trp missense_variant Exon 10 of 15 5 NM_001110199.3 ENSP00000480851.1 A0A087WXA3
SRRM3ENST00000464752.1 linkc.-21C>T upstream_gene_variant 2 ENSP00000483698.1 A0A087X0W5

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
152024
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000252
AC:
6
AN:
238074
Hom.:
0
AF XY:
0.0000309
AC XY:
4
AN XY:
129654
show subpopulations
Gnomad AFR exome
AF:
0.000139
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000699
Gnomad FIN exome
AF:
0.0000467
Gnomad NFE exome
AF:
0.00000913
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000166
AC:
24
AN:
1449526
Hom.:
0
Cov.:
30
AF XY:
0.0000194
AC XY:
14
AN XY:
720772
show subpopulations
Gnomad4 AFR exome
AF:
0.000276
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000597
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.00000723
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152142
Hom.:
0
Cov.:
30
AF XY:
0.0000538
AC XY:
4
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000336
Hom.:
0
Bravo
AF:
0.0000680
ExAC
AF:
0.0000332
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.748C>T (p.R250W) alteration is located in exon 10 (coding exon 9) of the SRRM3 gene. This alteration results from a C to T substitution at nucleotide position 748, causing the arginine (R) at amino acid position 250 to be replaced by a tryptophan (W). 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
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
22
DANN
Uncertain
0.99
Eigen
Benign
-0.093
Eigen_PC
Benign
0.041
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.076
T
MetaSVM
Benign
-0.99
T
PrimateAI
Benign
0.41
T
Sift4G
Uncertain
0.059
T
Vest4
0.28
MVP
0.043
ClinPred
0.29
T
GERP RS
3.9
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs560787592; hg19: chr7-75894704; API