11-93370184-C-A

Variant names:

• chr11-93370184-C-A
• rs778258481
• NM_181645.4:c.544C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181645.4(DEUP1):​c.544C>A​(p.Gln182Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000754 in 1,326,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: DEUP1 NM_181645.4 missense, splice_region
• Scores: Splicing: ADA: 0.9220
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

DEUP1 (HGNC:26344): (deuterosome assembly protein 1) Enables identical protein binding activity. Predicted to be involved in centriole replication and de novo centriole assembly involved in multi-ciliated epithelial cell differentiation. Predicted to be located in cytoplasm. Predicted to be integral component of membrane. Predicted to be active in centriole and deuterosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35397074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181645.4. 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
	DEUP1	NM_181645.4	MANE Select	c.544C>A	p.Gln182Lys	missense splice_region	Exon 6 of 14	NP_857596.2	Q05D60-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEUP1	ENST00000298050.9	TSL:5 MANE Select	c.544C>A	p.Gln182Lys	missense splice_region	Exon 6 of 14	ENSP00000298050.3	Q05D60-1
	DEUP1	ENST00000531792.5	TSL:1	c.544C>A	p.Gln182Lys	missense splice_region	Exon 6 of 11	ENSP00000433537.2	A0A088AWP1
	DEUP1	ENST00000530862.6	TSL:2	c.481C>A	p.Gln161Lys	missense splice_region	Exon 6 of 13	ENSP00000431946.3	E9PIY2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000463 AC: 1 AN: 216062 AF XY: 0.00000863

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000625

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 10 AN: 1326368 Hom.: 0 Cov.: 20 AF XY: 0.00000753 AC XY: 5 AN XY: 664220

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30770

American (AMR) AF: 0.0000242 AC: 1 AN: 41296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24942

East Asian (EAS) AF: 0.0000517 AC: 2 AN: 38648

South Asian (SAS) AF: 0.00 AC: 0 AN: 79646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5468

European-Non Finnish (NFE) AF: 0.00000100 AC: 1 AN: 997240

Other (OTH) AF: 0.000107 AC: 6 AN: 55922

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000830110), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.24
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.079	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.28		Gain of methylation at Q182 (P = 0.0091)
MVP		0.48
MPC		0.18
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.54
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.92
dbscSNV1_RF	Pathogenic	0.79
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

Other links and lift over

dbSNP: rs778258481; hg19: chr11-93103350;