Genetic Variant SRRT:p.Asp119Asp (chr7-100881764-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015908.6(SRRT):c.357C>T(p.Asp119Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,613,596 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 13 hom. )

Consequence

SRRT
NM_015908.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53

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]

SRRT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-100881764-C-T is Benign according to our data. Variant chr7-100881764-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657775.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.53 with no splicing effect.

BS2

High AC in GnomAd4 at 366 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRRT	NM_015908.6 link	c.357C>T	p.Asp119Asp	synonymous_variant	Exon 4 of 20	ENST00000611405.5	NP_056992.4	Q9BXP5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRRT	ENST00000611405.5 link	c.357C>T	p.Asp119Asp	synonymous_variant	Exon 4 of 20	1	NM_015908.6	ENSP00000480421.1		Q9BXP5-1
SRRT	ENST00000614484.4 link	c.357C>T	p.Asp119Asp	synonymous_variant	Exon 4 of 20	1		ENSP00000481173.1		Q9BXP5-3

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

367

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00372

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00286

AC:

702

AN:

245344

Hom.:

AF XY:

0.00280

AC XY:

374

AN XY:

133680

show subpopulations

Gnomad AFR exome

AF:

0.000524

Gnomad AMR exome

AF:

0.00374

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00399

Gnomad NFE exome

AF:

0.00373

Gnomad OTH exome

AF:

0.00732

GnomAD4 exome

AF:

0.00340

AC:

4973

AN:

1461274

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

2406

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00356

Gnomad4 ASJ exome

AF:

0.00195

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00383

Gnomad4 NFE exome

AF:

0.00389

Gnomad4 OTH exome

AF:

0.00331

GnomAD4 genome

AF:

0.00240

AC:

366

AN:

152322

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00372

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000833

Hom.:

Bravo

AF:

0.00233

EpiCase

AF:

0.00393

EpiControl

AF:

0.00379

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SRRT: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.7

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over