chr1-212065019-C-T

Variant names:

• chr1-212065019-C-T
• rs189644922
• NM_016448.4:c.629C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_016448.4(DTL):​c.629C>T​(p.Ala210Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,611,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (2 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: DTL NM_016448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07
• Publications: 1 publications found

Genes affected

DTL (HGNC:30288): (denticleless E3 ubiquitin protein ligase homolog) Contributes to ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of G2/M transition of mitotic cell cycle; and translesion synthesis. Located in centrosome; cytosol; and nuclear lumen. Part of Cul4A-RING E3 ubiquitin ligase complex and Cul4B-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3094132).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016448.4. 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
	DTL	NM_016448.4	MANE Select	c.629C>T	p.Ala210Val	missense	Exon 7 of 15	NP_057532.4	Q9NZJ0-1
	DTL	NM_001286230.2		c.503C>T	p.Ala168Val	missense	Exon 6 of 14	NP_001273159.2	F5GZ90
	DTL	NM_001286229.2		c.-81C>T		5_prime_UTR	Exon 6 of 13	NP_001273158.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTL	ENST00000366991.5	TSL:1 MANE Select	c.629C>T	p.Ala210Val	missense	Exon 7 of 15	ENSP00000355958.4	Q9NZJ0-1
	DTL	ENST00000935628.1		c.677C>T	p.Ala226Val	missense	Exon 8 of 16	ENSP00000605687.1
	DTL	ENST00000935625.1		c.629C>T	p.Ala210Val	missense	Exon 7 of 15	ENSP00000605684.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152190 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251116 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1459450 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726198

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.000224 AC: 10 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109876

Other (OTH) AF: 0.000116 AC: 7 AN: 60288

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152308 Hom.: 2 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.000850 AC: 13 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000223

ExAC AF: 0.00000824 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	Uncertain	0.44
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	-0.078	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.32
Sift	Benign	0.075	T
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.72
MVP		0.84
MPC		0.59
ClinPred		0.71	D
GERP RS		5.4
Varity_R		0.20
gMVP		0.69
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs189644922; hg19: chr1-212238361;