Variant chr19-41354391-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000539627.5(TMEM91):c.-30+3189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 590,170 control chromosomes in the GnomAD database, including 133,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36451 hom., cov: 31)

Exomes 𝑓: 0.66 ( 96677 hom. )

Consequence

TMEM91
ENST00000539627.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.81

Variant links:

Genes affected

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:

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:

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 (BayesDel_noAF=-0.91).

BP6

Variant 19-41354391-A-G is Benign according to our data. Variant chr19-41354391-A-G is described in ClinVar as [Benign]. Clinvar id is 39302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	Effect	MANE	Protein
B9D2	NM_030578.4 linkuse as main transcript	downstream_gene_variant	ENST00000243578.8	NP_085055.2
B9D2	XM_011527349.3 linkuse as main transcript	downstream_gene_variant		XP_011525651.1
B9D2	XM_011527350.3 linkuse as main transcript	downstream_gene_variant		XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
TMEM91	ENST00000539627.5 linkuse as main transcript	c.-30+3189A>G	intron_variant	1		ENSP00000441900
TMEM91	ENST00000604123.5 linkuse as main transcript	c.142+76A>G	intron_variant	3		ENSP00000474871
B9D2	ENST00000243578.8 linkuse as main transcript		downstream_gene_variant	1	NM_030578.4	ENSP00000243578	P1
B9D2	ENST00000675972.1 linkuse as main transcript		downstream_gene_variant			ENSP00000501911	P1

Frequencies

GnomAD3 genomes

AF:

0.687

AC:

104346

AN:

151848

Hom.:

36420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.816

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.445

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.744

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.659

AC:

288820

AN:

438204

Hom.:

96677

Cov.:

AF XY:

0.655

AC XY:

150231

AN XY:

229484

show subpopulations

Gnomad4 AFR exome

AF:

0.758

Gnomad4 AMR exome

AF:

0.545

Gnomad4 ASJ exome

AF:

0.534

Gnomad4 EAS exome

AF:

0.486

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.754

Gnomad4 NFE exome

AF:

0.687

Gnomad4 OTH exome

AF:

0.650

GnomAD4 genome

AF:

0.687

AC:

104435

AN:

151966

Hom.:

36451

Cov.:

AF XY:

0.684

AC XY:

50765

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.763

Gnomad4 AMR

AF:

0.571

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.445

Gnomad4 SAS

AF:

0.622

Gnomad4 FIN

AF:

0.744

Gnomad4 NFE

AF:

0.688

Gnomad4 OTH

AF:

0.642

Alfa

AF:

0.673

Hom.:

62689

Bravo

AF:

0.677

Asia WGS

AF:

0.548

AC:

1904

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2020	This variant is associated with the following publications: (PMID: 23703862, 15175276, 21761116, 22282866, 16207846, 21679448, 18670143, 19536820, 16896927, 17333284, 9887336, 19614955, 18547814, 20232138, 14597484, 19096005) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.6

DANN

Benign

0.48

Splicing

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