Variant 5-14600995-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_019018.3(OTULINL):c.95C>G(p.Ala32Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

OTULINL
NM_019018.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.674

Variant links:

Genes affected

OTULINL (HGNC:25629): (OTU deubiquitinase with linear linkage specificity like) Located in cytoplasm. Is extrinsic component of endoplasmic reticulum membrane. Colocalizes with nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

OTULINL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10273999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OTULINL	NM_019018.3 linkuse as main transcript	c.95C>G	p.Ala32Gly	missense_variant	2/8	ENST00000274217.4	NP_061891.1
OTULINL	XM_047417322.1 linkuse as main transcript	c.8C>G	p.Ala3Gly	missense_variant	4/10		XP_047273278.1
OTULINL	XM_047417323.1 linkuse as main transcript	c.8C>G	p.Ala3Gly	missense_variant	3/9		XP_047273279.1
OTULINL	XR_925623.3 linkuse as main transcript	n.198C>G		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTULINL	ENST00000274217.4 linkuse as main transcript	c.95C>G	p.Ala32Gly	missense_variant	2/8	1	NM_019018.3	ENSP00000274217	P1
OTULINL	ENST00000513825.1 linkuse as main transcript	n.31C>G		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1408488

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695260

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.22e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.95C>G (p.A32G) alteration is located in exon 2 (coding exon 2) of the FAM105A gene. This alteration results from a C to G substitution at nucleotide position 95, causing the alanine (A) at amino acid position 32 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.011

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.65

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

REVEL

Benign

0.020

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.13

Vest4

0.13

MutPred

0.21

Loss of helix (P = 0.028);

MVP

0.15

MPC

0.23

ClinPred

0.16

GERP RS

3.0

Varity_R

0.12

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over