7-100884392-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015908.6(SRRT):​c.782C>T​(p.Thr261Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000422 in 1,613,236 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SRRT
NM_015908.6 missense

Scores

3
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.81
Variant links:
Genes affected
SRRT (HGNC:24101): (serrate, RNA effector molecule) Enables mRNA cap binding complex binding activity and protein-macromolecule adaptor activity. Involved in primary miRNA processing. Located in nucleoplasm. Part of ribonucleoprotein complex. [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 -4 ACMG points.

BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRRTNM_015908.6 linkc.782C>T p.Thr261Met missense_variant Exon 7 of 20 ENST00000611405.5 NP_056992.4 Q9BXP5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRRTENST00000611405.5 linkc.782C>T p.Thr261Met missense_variant Exon 7 of 20 1 NM_015908.6 ENSP00000480421.1 Q9BXP5-1
SRRTENST00000614484.4 linkc.782C>T p.Thr261Met missense_variant Exon 7 of 20 1 ENSP00000481173.1 Q9BXP5-3

Frequencies

GnomAD3 genomes
AF:
0.0000593
AC:
9
AN:
151746
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.0000948
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
249804
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135180
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000582
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000404
AC:
59
AN:
1461490
Hom.:
0
Cov.:
37
AF XY:
0.0000399
AC XY:
29
AN XY:
727036
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.0000360
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000593
AC:
9
AN:
151746
Hom.:
0
Cov.:
32
AF XY:
0.0000675
AC XY:
5
AN XY:
74102
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000197
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.0000948
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000174
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.782C>T (p.T261M) alteration is located in exon 7 (coding exon 6) of the SRRT gene. This alteration results from a C to T substitution at nucleotide position 782, causing the threonine (T) at amino acid position 261 to be replaced by a methionine (M). 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
0.28
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.74
.;.;.;D
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.51
D;D;D;D
MetaSVM
Benign
-0.48
T
MutationAssessor
Uncertain
2.5
M;M;M;M
PrimateAI
Uncertain
0.74
T
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.69
MVP
0.41
ClinPred
0.88
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.57
gMVP
0.72

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs778464271; hg19: chr7-100482013; API