chr19-41354800-C-A

Variant names:

• chr19-41354800-C-A
• rs749813956
• NM_030578.4:c.428G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030578.4(B9D2):​c.428G>T​(p.Gly143Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: B9D2 NM_030578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.30

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D2	NM_030578.4	c.428G>T	p.Gly143Val	missense_variant	Exon 4 of 4	ENST00000243578.8	NP_085055.2
B9D2	XM_011527349.3	c.428G>T	p.Gly143Val	missense_variant	Exon 4 of 4		XP_011525651.1
B9D2	XM_011527350.3	c.269G>T	p.Gly90Val	missense_variant	Exon 3 of 3		XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D2	ENST00000243578.8	c.428G>T	p.Gly143Val	missense_variant	Exon 4 of 4	1	NM_030578.4	ENSP00000243578.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.60
Sift	Benign	0.19	T
Sift4G	Benign	0.14	T
Polyphen		0.88	P
Vest4		0.84
MutPred		0.71		Gain of sheet (P = 0.0344);
MVP		0.73
MPC		0.80
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.77
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs749813956; hg19: chr19-41860705;