Genetic Variant SRRM3:p.Pro167Ser (chr7-76260151-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001110199.3(SRRM3):c.499C>T(p.Pro167Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000475 in 1,537,444 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000048 ( 2 hom. )

Consequence

SRRM3
NM_001110199.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Publications

0 publications found

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]

SRRM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024600238).

BS2

High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001110199.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM3	NM_001110199.3	MANE Select	c.499C>T	p.Pro167Ser	missense	Exon 5 of 15	NP_001103669.1	A0A087WXA3
	SRRM3	NM_001291831.2		c.499C>T	p.Pro167Ser	missense	Exon 5 of 16	NP_001278760.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRRM3	ENST00000611745.2	TSL:5 MANE Select	c.499C>T	p.Pro167Ser	missense	Exon 5 of 15	ENSP00000480851.1	A0A087WXA3
	SRRM3	ENST00000479294.2	TSL:2	n.*117C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000464

AC:

AN:

150866

Hom.:

Cov.:

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:

0.000849

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000194

AC:

AN:

139486

AF XY:

0.000276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000840

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.000254

GnomAD4 exome

AF:

0.0000476

AC:

AN:

1386466

Hom.:

Cov.:

AF XY:

0.0000760

AC XY:

AN XY:

684342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30070

American (AMR)

AF:

0.000114

AC:

AN:

34968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24656

East Asian (EAS)

AF:

0.00

AC:

AN:

34344

South Asian (SAS)

AF:

0.000727

AC:

AN:

78358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4534

European-Non Finnish (NFE)

AF:

0.00000279

AC:

AN:

1075204

Other (OTH)

AF:

0.0000349

AC:

AN:

57280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.0000464

AC:

AN:

150978

Hom.:

Cov.:

AF XY:

0.0000543

AC XY:

AN XY:

73716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41210

American (AMR)

AF:

0.000197

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5018

South Asian (SAS)

AF:

0.000849

AC:

AN:

4712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67630

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000157

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

0.23

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.64

PhyloP100

2.8

PrimateAI

Pathogenic

0.86

Sift4G

Benign

0.20

Vest4

0.22

MVP

0.043

ClinPred

0.12

GERP RS

4.0

gMVP

0.11

Mutation Taster

=92/8

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over