dbSNP rs17391197: TM9SF3:c.1703-73T>C (chr10-96522403-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020123.4(TM9SF3):c.1703-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,145,324 control chromosomes in the GnomAD database, including 12,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1111 hom., cov: 32)

Exomes 𝑓: 0.14 ( 10932 hom. )

Consequence

TM9SF3
NM_020123.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.575

Publications

5 publications found

Variant links:

Genes affected

TM9SF3 (HGNC:21529): (transmembrane 9 superfamily member 3) Predicted to be involved in protein localization to membrane. Predicted to be located in exocytic vesicle. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TM9SF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020123.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TM9SF3	NM_020123.4	MANE Select	c.1703-73T>C		intron	N/A	NP_064508.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TM9SF3	ENST00000371142.9	TSL:1 MANE Select	c.1703-73T>C	intron	N/A	ENSP00000360184.4
TM9SF3	ENST00000485093.1	TSL:5	n.354-73T>C	intron	N/A
TM9SF3	ENST00000649367.1		n.2041-73T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16828

AN:

151542

Hom.:

1108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.0147

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.143

AC:

141750

AN:

993664

Hom.:

10932

AF XY:

0.143

AC XY:

72062

AN XY:

504038

show subpopulations

African (AFR)

AF:

0.0628

AC:

1233

AN:

19622

American (AMR)

AF:

0.0605

AC:

1209

AN:

19974

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

2857

AN:

19648

East Asian (EAS)

AF:

0.0115

AC:

359

AN:

31112

South Asian (SAS)

AF:

0.127

AC:

7441

AN:

58670

European-Finnish (FIN)

AF:

0.143

AC:

6865

AN:

48090

Middle Eastern (MID)

AF:

0.0969

AC:

442

AN:

4562

European-Non Finnish (NFE)

AF:

0.154

AC:

115544

AN:

748442

Other (OTH)

AF:

0.133

AC:

5800

AN:

43544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5787

11573

17360

23146

28933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3598

7196

10794

14392

17990

<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:

0.111

AC:

16832

AN:

151660

Hom.:

1111

Cov.:

AF XY:

0.110

AC XY:

8135

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.0641

AC:

2655

AN:

41430

American (AMR)

AF:

0.0764

AC:

1162

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

516

AN:

3458

East Asian (EAS)

AF:

0.0143

AC:

AN:

5174

South Asian (SAS)

AF:

0.115

AC:

552

AN:

4816

European-Finnish (FIN)

AF:

0.126

AC:

1327

AN:

10566

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10244

AN:

67702

Other (OTH)

AF:

0.106

AC:

223

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

755

1511

2266

3022

3777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<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:

0.126

Hom.:

779

Bravo

AF:

0.105

Asia WGS

AF:

0.0690

AC:

243

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.1

(source)

DANN

Benign

0.76

PhyloP100

-0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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