dbSNP rs11466314: TMEM91:c.-30+3129C>T (chr19-41354331-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 ENST00000539627.5(TMEM91):c.-30+3129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 563,110 control chromosomes in the GnomAD database, including 5 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 0.0043 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 1 hom. )

Consequence

TMEM91
ENST00000539627.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.957

Publications

17 publications found

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:

ENSG00000255730 (HGNC:):

ENSG00000255730 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 Gene-Disease associations (from GenCC):

Meckel syndrome, type 10
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
ciliopathy
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

B9D2 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 (BayesDel_noAF=-0.74).

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
B9D2	NM_030578.4 link	c.*369G>A	downstream_gene_variant	ENST00000243578.8	NP_085055.2
B9D2	XM_011527349.3 link	c.*369G>A	downstream_gene_variant		XP_011525651.1
B9D2	XM_011527350.3 link	c.*369G>A	downstream_gene_variant		XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D2	ENST00000243578.8 link	c.*369G>A		downstream_gene_variant		1	NM_030578.4	ENSP00000243578.2

Frequencies

GnomAD3 genomes

AF:

0.00427

AC:

649

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00221

AC:

107

AN:

48466

AF XY:

0.00215

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000107

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000538

AC:

221

AN:

410966

Hom.:

Cov.:

AF XY:

0.000545

AC XY:

117

AN XY:

214702

show subpopulations

African (AFR)

AF:

0.0141

AC:

168

AN:

11950

American (AMR)

AF:

0.00112

AC:

AN:

16926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12868

East Asian (EAS)

AF:

0.00

AC:

AN:

29974

South Asian (SAS)

AF:

0.000109

AC:

AN:

36856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28036

Middle Eastern (MID)

AF:

0.00109

AC:

AN:

1836

European-Non Finnish (NFE)

AF:

0.0000161

AC:

AN:

248316

Other (OTH)

AF:

0.000992

AC:

AN:

24204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.00427

AC:

650

AN:

152144

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0149

AC:

617

AN:

41492

American (AMR)

AF:

0.00150

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67968

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00881

Hom.:

Bravo

AF:

0.00509

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.9

(source)

DANN

Benign

0.79

PhyloP100

0.96

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over