Genetic Variant NM_015908.6:c.797G>A (chr7-100884407-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015908.6(SRRT):c.797G>A(p.Arg266His) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,490 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: 0.0000055 ( 0 hom. )

Consequence

SRRT
NM_015908.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25998202).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015908.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRRT	NM_015908.6	MANE Select	c.797G>A	p.Arg266His	missense	Exon 7 of 20	NP_056992.4
SRRT	NM_001128852.2		c.797G>A	p.Arg266His	missense	Exon 7 of 20	NP_001122324.1	Q9BXP5-3
SRRT	NM_001128853.2		c.797G>A	p.Arg266His	missense	Exon 7 of 20	NP_001122325.1	Q9BXP5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SRRT	ENST00000611405.5	TSL:1 MANE Select	c.797G>A	p.Arg266His	missense	Exon 7 of 20	ENSP00000480421.1	Q9BXP5-1
SRRT	ENST00000614484.4	TSL:1	c.797G>A	p.Arg266His	missense	Exon 7 of 20	ENSP00000481173.1	Q9BXP5-3
SRRT	ENST00000618262.4	TSL:1	c.797G>A	p.Arg266His	missense	Exon 7 of 20	ENSP00000478341.1	Q9BXP5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000400

AC:

AN:

249696

AF XY:

0.0000444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000382

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727026

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.000101

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111898

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.012

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.4

PhyloP100

3.6

PrimateAI

Uncertain

0.67

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.46

MutPred

0.19

Gain of catalytic residue at L268 (P = 0.048)

MVP

0.29

ClinPred

0.47

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.37

Mutation Taster

=61/39

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over