rs76976586

Variant names:

• chr14-44904481-C-G
• rs76976586
• NM_001017923.2:c.701C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-44904481-C-G
• chr14-44904481-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017923.2(DORIP1):​c.701C>G​(p.Ser234Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S234F) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DORIP1 NM_001017923.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2276757).

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.701C>G	p.Ser234Cys	missense	Exon 4 of 5	NP_001017923.1
	LOC101927418	NR_110050.1		n.162-5168G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DORIP1	ENST00000325192.8	TSL:1 MANE Select	c.701C>G	p.Ser234Cys	missense	Exon 4 of 5	ENSP00000326846.3	Q4W4Y0
	DORIP1	ENST00000866783.1		c.701C>G	p.Ser234Cys	missense	Exon 3 of 4	ENSP00000536842.1
	DORIP1	ENST00000866784.1		c.701C>G	p.Ser234Cys	missense	Exon 5 of 6	ENSP00000536843.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250210 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459832 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726108

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110940

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.6
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.10
Sift	Benign	0.060	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.50
MutPred		0.33		Gain of catalytic residue at Q230 (P = 0.0032)
MVP		0.32
MPC		0.050
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.38
gMVP		0.48
Mutation Taster		=89/11	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: rs76976586; hg19: chr14-45373684;