rs148239437

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003611.3(OFD1):c.2044A>C(p.Ile682Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,166,792 control chromosomes in the GnomAD database, including 3 homozygotes. There are 121 hemizygotes in GnomAD. 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 0.0020 ( 2 hom., 65 hem., cov: 22)

Exomes 𝑓: 0.00019 ( 1 hom. 56 hem. )

Consequence

OFD1
NM_003611.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.340

Variant links:

Genes affected

OFD1 (HGNC:2567): (OFD1 centriole and centriolar satellite protein) This gene is located on the X chromosome and encodes a centrosomal protein. A knockout mouse model has been used to study the effect of mutations in this gene. The mouse gene is also located on the X chromosome, however, unlike the human gene it is not subject to X inactivation. Mutations in this gene are associated with oral-facial-digital syndrome type I and Simpson-Golabi-Behmel syndrome type 2. Many pseudogenes have been identified; a single pseudogene is found on chromosome 5 while as many as fifteen have been found on the Y chromosome. [provided by RefSeq, Aug 2016]

OFD1 links:

OFD1 (HGNC:):

OFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039521456).

BP6

Variant X-13760504-A-C is Benign according to our data. Variant chrX-13760504-A-C is described in ClinVar as [Benign]. Clinvar id is 239545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00202 (226/111788) while in subpopulation AFR AF= 0.00705 (217/30779). AF 95% confidence interval is 0.00628. There are 2 homozygotes in gnomad4. There are 65 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OFD1	NM_003611.3 linkuse as main transcript	c.2044A>C	p.Ile682Leu	missense_variant	16/23	ENST00000340096.11	NP_003602.1	O75665-1E9KL37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OFD1	ENST00000340096.11 linkuse as main transcript	c.2044A>C	p.Ile682Leu	missense_variant	16/23	1	NM_003611.3	ENSP00000344314.6		O75665-1

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

226

AN:

111732

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

AN XY:

33908

show subpopulations

Gnomad AFR

AF:

0.00707

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000566

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:

0.0000377

Gnomad OTH

AF:

0.000677

GnomAD3 exomes

AF:

0.000725

AC:

105

AN:

144828

Hom.:

AF XY:

0.000583

AC XY:

AN XY:

48058

show subpopulations

Gnomad AFR exome

AF:

0.00770

Gnomad AMR exome

AF:

0.000397

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000923

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000297

GnomAD4 exome

AF:

0.000186

AC:

196

AN:

1055004

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

341480

show subpopulations

Gnomad4 AFR exome

AF:

0.00666

Gnomad4 AMR exome

AF:

0.000435

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000214

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000486

Gnomad4 OTH exome

AF:

0.000340

GnomAD4 genome

AF:

0.00202

AC:

226

AN:

111788

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

AN XY:

33974

show subpopulations

Gnomad4 AFR

AF:

0.00705

Gnomad4 AMR

AF:

0.000565

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.000668

Alfa

AF:

0.000703

Hom.:

Bravo

AF:

0.00241

ESP6500AA

AF:

0.00600

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000720

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 24, 2019	- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 22, 2019

- -

Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.012

DANN

Benign

0.79

DEOGEN2

Benign

0.12

T;.;.

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.32

T;T;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

2.0

M;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.11

B;B;B

Vest4

0.16

MVP

0.64

MPC

0.14

ClinPred

0.0044

GERP RS

-3.0

Varity_R

0.068

gMVP

0.067

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over