14-44900633-A-T

Variant names:

• chr14-44900633-A-T
• rs61978647
• NM_001017923.2:c.198A>T

Variant summary

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

The NM_001017923.2(DORIP1):​c.198A>T​(p.Leu66Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,678 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L66L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DORIP1 NM_001017923.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 0 publications found

Genes affected

DORIP1 (HGNC:19834): (chromosome 14 open reading frame 28)

RRAGAP1-AS1 (HGNC:55445): (RRAGAP1 antisense RNA 1)

LOC101927418 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017923.2. 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
	DORIP1	NM_001017923.2	MANE Select	c.198A>T	p.Leu66Phe	missense	Exon 2 of 5	NP_001017923.1
	LOC101927418	NR_110050.1		n.162-1320T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DORIP1	ENST00000325192.8	TSL:1 MANE Select	c.198A>T	p.Leu66Phe	missense	Exon 2 of 5	ENSP00000326846.3	Q4W4Y0
	DORIP1	ENST00000866783.1		c.198A>T	p.Leu66Phe	missense	Exon 1 of 4	ENSP00000536842.1
	DORIP1	ENST00000866784.1		c.198A>T	p.Leu66Phe	missense	Exon 3 of 6	ENSP00000536843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456678 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724498

African (AFR) AF: 0.00 AC: 0 AN: 32978

American (AMR) AF: 0.00 AC: 0 AN: 43462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 84888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110596

Other (OTH) AF: 0.00 AC: 0 AN: 60152

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.69
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.32		Gain of catalytic residue at V68 (P = 0.002)
MVP		0.42
MPC		0.30
ClinPred		0.99	D
GERP RS		-4.5
Varity_R		0.73
gMVP		0.63
Mutation Taster		=50/50

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: rs61978647; hg19: chr14-45369836;