Genetic Variant SRRT:p.Asp306Ala (chr7-100884527-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015908.6(SRRT):c.917A>C(p.Asp306Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000293 in 1,432,864 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: not found (cov: 28)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SRRT
NM_015908.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06639719).

BS2

High AC in GnomAdExome4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRRT	NM_015908.6 link	c.917A>C	p.Asp306Ala	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
SRRT	ENST00000611405.5 link	c.917A>C	p.Asp306Ala	missense_variant	Exon 7 of 20	1	NM_015908.6	ENSP00000480421.1		Q9BXP5-1
SRRT	ENST00000614484.4 link	c.917A>C	p.Asp306Ala	missense_variant	Exon 7 of 20	1		ENSP00000481173.1		Q9BXP5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249596

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS 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:

0.0000293

AC:

AN:

1432864

Hom.:

Cov.:

AF XY:

0.0000337

AC XY:

AN XY:

712626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00114

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.917A>C (p.D306A) alteration is located in exon 7 (coding exon 6) of the SRRT gene. This alteration results from a A to C substitution at nucleotide position 917, causing the aspartic acid (D) at amino acid position 306 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;.;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.066

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L;L

PrimateAI

Uncertain

0.51

Sift4G

Benign

0.085

T;T;T;T

Polyphen

0.34

B;B;B;B

Vest4

0.32

MutPred

0.23

Gain of MoRF binding (P = 0.0221);Gain of MoRF binding (P = 0.0221);Gain of MoRF binding (P = 0.0221);Gain of MoRF binding (P = 0.0221);

MVP

0.093

ClinPred

0.075

GERP RS

3.9

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.2

Varity_R

0.068

gMVP

0.30

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

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