chr1-11501143-C-G

Variant names:

• chr1-11501143-C-G
• rs3738159
• NM_020780.2:c.151C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020780.2(DISP3):​c.151C>G​(p.Leu51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,926 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (15 hom.)
• Consequence: DISP3 NM_020780.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.104
• Publications: 6 publications found

Genes affected

DISP3 (HGNC:29251): (dispatched RND transporter family member 3) Involved in negative regulation of neuron differentiation; positive regulation of lipid metabolic process; and positive regulation of neural precursor cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285833 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027417839).
• BP6: Variant 1-11501143-C-G is Benign according to our data. Variant chr1-11501143-C-G is described in ClinVar as Benign. ClinVar VariationId is 721203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00133 (203/152288) while in subpopulation EAS AF = 0.0244 (126/5162). AF 95% confidence interval is 0.0209. There are 4 homozygotes in GnomAd4. There are 107 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020780.2. 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
	DISP3	NM_020780.2	MANE Select	c.151C>G	p.Leu51Val	missense	Exon 2 of 21	NP_065831.1	Q9P2K9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISP3	ENST00000294484.7	TSL:1 MANE Select	c.151C>G	p.Leu51Val	missense	Exon 2 of 21	ENSP00000294484.6	Q9P2K9-1
	DISP3	ENST00000922105.1		c.151C>G	p.Leu51Val	missense	Exon 2 of 21	ENSP00000592164.1
	DISP3	ENST00000922103.1		c.151C>G	p.Leu51Val	missense	Exon 2 of 21	ENSP00000592162.1

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 203 AN: 152170 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00351 AC: 873 AN: 248574 AF XY: 0.00309

Gnomad AFR exome AF: 0.000583

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00340

Gnomad EAS exome AF: 0.0237

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.00232

GnomAD4 exome AF: 0.00106 AC: 1547 AN: 1461638 Hom.: 15 Cov.: 31 AF XY: 0.00102 AC XY: 739 AN XY: 727118

African (AFR) AF: 0.000358 AC: 12 AN: 33476

American (AMR) AF: 0.00888 AC: 397 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00257 AC: 67 AN: 26100

East Asian (EAS) AF: 0.0228 AC: 906 AN: 39698

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111906

Other (OTH) AF: 0.00132 AC: 80 AN: 60384

GnomAD4 genome AF: 0.00133 AC: 203 AN: 152288 Hom.: 4 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74454

African (AFR) AF: 0.000505 AC: 21 AN: 41562

American (AMR) AF: 0.00229 AC: 35 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.0244 AC: 126 AN: 5162

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000893 Hom.: 0

Bravo AF: 0.00197

ExAC AF: 0.00309 AC: 373

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DISP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.3
DANN	Benign	0.90
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.10
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.017
Sift	Benign	0.042	D
Sift4G	Benign	0.19	T
Polyphen		0.18	B
Vest4		0.13
MVP		0.076
MPC		0.55
ClinPred		0.0059	T
GERP RS		-1.7
Varity_R		0.069
gMVP		0.18
Mutation Taster		=97/3	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: rs3738159; hg19: chr1-11561200;