rs11466314

Variant names:

• chr19-41354331-C-T
• rs11466314
• ENST00000539627.5:c.-30+3129C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957
• Publications: 17 publications found

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]

ENSG00000255730 (HGNC:):

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

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539627.5. 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
	B9D2	NM_030578.4	MANE Select	c.*369G>A		downstream_gene	N/A	NP_085055.2	Q9BPU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM91	ENST00000539627.5	TSL:1	c.-30+3129C>T		intron	N/A	ENSP00000441900.1	F5GWC9
	TMEM91	ENST00000604123.5	TSL:3	c.142+16C>T		intron	N/A	ENSP00000474871.1	S4R3Y8
	TMEM91	ENST00000889861.1		c.-30+3129C>T		intron	N/A	ENSP00000559920.1

Frequencies

GnomAD3 genomes AF: 0.00427 AC: 649 AN: 152026 Hom.: 4 Cov.: 32

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

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.: 1 Cov.: 0 AF XY: 0.000545 AC XY: 117 AN XY: 214702

African (AFR) AF: 0.0141 AC: 168 AN: 11950

American (AMR) AF: 0.00112 AC: 19 AN: 16926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12868

East Asian (EAS) AF: 0.00 AC: 0 AN: 29974

South Asian (SAS) AF: 0.000109 AC: 4 AN: 36856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28036

Middle Eastern (MID) AF: 0.00109 AC: 2 AN: 1836

European-Non Finnish (NFE) AF: 0.0000161 AC: 4 AN: 248316

Other (OTH) AF: 0.000992 AC: 24 AN: 24204

GnomAD4 genome AF: 0.00427 AC: 650 AN: 152144 Hom.: 4 Cov.: 32 AF XY: 0.00422 AC XY: 314 AN XY: 74384

African (AFR) AF: 0.0149 AC: 617 AN: 41492

American (AMR) AF: 0.00150 AC: 23 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67968

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00881 Hom.: 3

Bravo AF: 0.00509

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		0.96
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11466314; hg19: chr19-41860236;