1-11502856-C-T

Variant names:

• chr1-11502856-C-T
• rs60362998
• NM_020780.2:c.1275C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_020780.2(DISP3):​c.1275C>T​(p.Phe425Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,614,002 control chromosomes in the GnomAD database, including 8,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1765 hom., cov: 33)
  • Exomes 𝑓: 0.081 (6490 hom.)
• Consequence: DISP3 NM_020780.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.384
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 1-11502856-C-T is Benign according to our data. Variant chr1-11502856-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060865.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.384 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

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.1275C>T	p.Phe425Phe	synonymous	Exon 3 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.1275C>T	p.Phe425Phe	synonymous	Exon 3 of 21	ENSP00000294484.6	Q9P2K9-1
	DISP3	ENST00000922105.1		c.1275C>T	p.Phe425Phe	synonymous	Exon 3 of 21	ENSP00000592164.1
	DISP3	ENST00000922103.1		c.1275C>T	p.Phe425Phe	synonymous	Exon 3 of 21	ENSP00000592162.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19334 AN: 152124 Hom.: 1757 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.0984 AC: 24537 AN: 249370 AF XY: 0.103

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.0401

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0384

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0700

Gnomad OTH exome AF: 0.0784

GnomAD4 exome AF: 0.0814 AC: 119008 AN: 1461760 Hom.: 6490 Cov.: 32 AF XY: 0.0849 AC XY: 61714 AN XY: 727176

African (AFR) AF: 0.262 AC: 8766 AN: 33478

American (AMR) AF: 0.0433 AC: 1937 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3145 AN: 26130

East Asian (EAS) AF: 0.0406 AC: 1610 AN: 39700

South Asian (SAS) AF: 0.199 AC: 17156 AN: 86240

European-Finnish (FIN) AF: 0.119 AC: 6383 AN: 53418

Middle Eastern (MID) AF: 0.130 AC: 750 AN: 5754

European-Non Finnish (NFE) AF: 0.0662 AC: 73580 AN: 1111938

Other (OTH) AF: 0.0941 AC: 5681 AN: 60390

GnomAD4 genome AF: 0.127 AC: 19362 AN: 152242 Hom.: 1765 Cov.: 33 AF XY: 0.130 AC XY: 9687 AN XY: 74444

African (AFR) AF: 0.251 AC: 10440 AN: 41524

American (AMR) AF: 0.0659 AC: 1008 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3472

East Asian (EAS) AF: 0.0455 AC: 236 AN: 5184

South Asian (SAS) AF: 0.199 AC: 958 AN: 4826

European-Finnish (FIN) AF: 0.128 AC: 1362 AN: 10612

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.0677 AC: 4607 AN: 68010

Other (OTH) AF: 0.109 AC: 230 AN: 2114

Alfa AF: 0.0942 Hom.: 838

Bravo AF: 0.123

Asia WGS AF: 0.141 AC: 491 AN: 3478

EpiCase AF: 0.0723

EpiControl AF: 0.0675

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DISP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.38
Mutation Taster		=74/26	polymorphism (auto)

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: rs60362998; hg19: chr1-11562913; COSMIC: COSV53833270;