19-41363487-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030578.4(B9D2):c.33A>G(p.Ile11Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,613,570 control chromosomes in the GnomAD database, including 380,889 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38333 hom., cov: 31)

Exomes 𝑓: 0.68 ( 342556 hom. )

Consequence

B9D2
NM_030578.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.146

Variant links:

Genes affected

B9D2 (HGNC:28636): (B9 domain containing 2) This gene encodes a B9 domain protein, which are exclusively found in ciliated organisms. The gene is upregulated during mucociliary differentiation, and the encoded protein localizes to basal bodies and cilia. Disrupting expression of this gene results in ciliogenesis defects. [provided by RefSeq, Oct 2009]

B9D2 links:

TMEM91 (HGNC:32393): (transmembrane protein 91) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM91 links:

ENSG00000255730 (HGNC:):

ENSG00000255730 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.400341E-7).

BP6

Variant 19-41363487-T-C is Benign according to our data. Variant chr19-41363487-T-C is described in ClinVar as [Benign]. Clinvar id is 261881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-41363487-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D2	NM_030578.4 link	c.33A>G	p.Ile11Met	missense_variant	Exon 2 of 4	ENST00000243578.8	NP_085055.2	Q9BPU9
B9D2	XM_011527349.3 link	c.33A>G	p.Ile11Met	missense_variant	Exon 2 of 4		XP_011525651.1	Q9BPU9
B9D2	XM_011527350.3 link	c.-72+471A>G		intron_variant	Intron 1 of 2		XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D2	ENST00000243578.8 link	c.33A>G	p.Ile11Met	missense_variant	Exon 2 of 4	1	NM_030578.4	ENSP00000243578.2		Q9BPU9

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

106611

AN:

151746

Hom.:

38297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.539

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.652

GnomAD3 exomes

AF:

0.643

AC:

161624

AN:

251252

Hom.:

53198

AF XY:

0.643

AC XY:

87295

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.838

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.542

Gnomad EAS exome

AF:

0.452

Gnomad SAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.722

Gnomad NFE exome

AF:

0.682

Gnomad OTH exome

AF:

0.644

GnomAD4 exome

AF:

0.681

AC:

995851

AN:

1461706

Hom.:

342556

Cov.:

AF XY:

0.677

AC XY:

492577

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.836

Gnomad4 AMR exome

AF:

0.531

Gnomad4 ASJ exome

AF:

0.533

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.614

Gnomad4 FIN exome

AF:

0.724

Gnomad4 NFE exome

AF:

0.698

Gnomad4 OTH exome

AF:

0.664

GnomAD4 genome

AF:

0.703

AC:

106707

AN:

151864

Hom.:

38333

Cov.:

AF XY:

0.697

AC XY:

51707

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.833

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.539

Gnomad4 EAS

AF:

0.445

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.716

Gnomad4 NFE

AF:

0.684

Gnomad4 OTH

AF:

0.650

Alfa

AF:

0.671

Hom.:

80931

Bravo

AF:

0.698

TwinsUK

AF:

0.707

AC:

2620

ALSPAC

AF:

0.703

AC:

2710

ESP6500AA

AF:

0.825

AC:

3637

ESP6500EA

AF:

0.673

AC:

5786

ExAC

AF:

0.655

AC:

79472

Asia WGS

AF:

0.551

AC:

1912

AN:

3478

EpiCase

AF:

0.656

EpiControl

AF:

0.658

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Meckel syndrome, type 10

Benign:3

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.070

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.064

MetaRNN

Benign

7.4e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.56

REVEL

Benign

0.081

Sift

Benign

0.19

Sift4G

Benign

0.11

Polyphen

0.0010

Vest4

0.014

MPC

0.24

ClinPred

0.0021

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.21

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