NM_030578.4:c.33A>C

Variant names:

• chr19-41363487-T-G
• rs2241714
• NM_030578.4:c.33A>C
• B9D2 p.Ile11Ile

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030578.4(B9D2):​c.33A>C​(p.Ile11Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: B9D2 NM_030578.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 0 publications found

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]

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:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.146 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030578.4. 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.33A>C	p.Ile11Ile	synonymous	Exon 2 of 4	NP_085055.2	Q9BPU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D2	ENST00000243578.8	TSL:1 MANE Select	c.33A>C	p.Ile11Ile	synonymous	Exon 2 of 4	ENSP00000243578.2	Q9BPU9
	TMEM91	ENST00000539627.5	TSL:1	c.-30+12285T>G		intron	N/A	ENSP00000441900.1	F5GWC9
	B9D2	ENST00000675972.1		c.33A>C	p.Ile11Ile	synonymous	Exon 2 of 4	ENSP00000501911.1	Q9BPU9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		-0.15
PromoterAI		0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2241714;

hg19: chr19-41869392;