21-36245332-T-C

Variant names:

• chr21-36245332-T-C
• rs4817788
• NM_001320714.2:c.3352T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001320714.2(DOP1B):​c.3352T>C​(p.Cys1118Arg) 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. 16/22 in silico tools predict 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: 33)
• Consequence: DOP1B NM_001320714.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 33 publications found

Genes affected

DOP1B (HGNC:1291): (DOP1 leucine zipper like protein B) Involved in cognition. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056341946).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320714.2. 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
	DOP1B	NM_001320714.2	MANE Select	c.3352T>C	p.Cys1118Arg	missense	Exon 19 of 37	NP_001307643.1	Q9Y3R5-1
	DOP1B	NM_005128.4		c.3352T>C	p.Cys1118Arg	missense	Exon 19 of 37	NP_005119.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOP1B	ENST00000691173.1	MANE Select	c.3352T>C	p.Cys1118Arg	missense	Exon 19 of 37	ENSP00000509598.1	Q9Y3R5-1
	DOP1B	ENST00000399151.3	TSL:1	c.3352T>C	p.Cys1118Arg	missense	Exon 19 of 37	ENSP00000382104.3	Q9Y3R5-1
	DOP1B	ENST00000943076.1		c.3352T>C	p.Cys1118Arg	missense	Exon 19 of 36	ENSP00000613135.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 120

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.7
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.035
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.056
MutPred		0.14		Loss of stability (P = 0.0459)
MVP		0.14
MPC		0.31
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.18
gMVP		0.42
Mutation Taster		=93/7	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

dbSNP: rs4817788; hg19: chr21-37617630;