chr10-119123507-C-T

Variant names:

• chr10-119123507-C-T
• NM_207009.4:c.632C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207009.4(DENND10):​c.632C>T​(p.Thr211Ile) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DENND10 NM_207009.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

Genes affected

DENND10 (HGNC:31793): (DENN domain containing 10) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endosome transport via multivesicular body sorting pathway; protein transport; and regulation of early endosome to late endosome transport. Located in late endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25200874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207009.4. 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
	DENND10	NM_207009.4	MANE Select	c.632C>T	p.Thr211Ile	missense	Exon 6 of 9	NP_996892.1	Q8TCE6-1
	DENND10	NM_001303111.2		c.608C>T	p.Thr203Ile	missense	Exon 7 of 10	NP_001290040.1	Q8TCE6-2
	DENND10	NM_001303112.2		c.413C>T	p.Thr138Ile	missense	Exon 6 of 9	NP_001290041.1	B4DNL9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND10	ENST00000361432.3	TSL:1 MANE Select	c.632C>T	p.Thr211Ile	missense	Exon 6 of 9	ENSP00000354688.2	Q8TCE6-1
	DENND10	ENST00000857543.1		c.587C>T	p.Thr196Ile	missense	Exon 6 of 9	ENSP00000527602.1
	DENND10	ENST00000857542.1		c.632C>T	p.Thr211Ile	missense	Exon 6 of 8	ENSP00000527601.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.32
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.056
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.0
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.029
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.014	D
Polyphen		0.37	B
Vest4		0.41
MutPred		0.34		Gain of helix (P = 0.1736)
MVP		0.32
MPC		0.52
ClinPred		0.82	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.23
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

hg19: chr10-120883019;