5-14601051-G-T

Position:

• chr5-14601051-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019018.3(OTULINL):​c.151G>T​(p.Ala51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,462 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OTULINL NM_019018.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.696

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047267944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTULINL	NM_019018.3	c.151G>T	p.Ala51Ser	missense_variant	2/8	ENST00000274217.4	NP_061891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTULINL	ENST00000274217.4	c.151G>T	p.Ala51Ser	missense_variant	2/8	1	NM_019018.3	ENSP00000274217	P1
OTULINL	ENST00000513825.1	n.87G>T		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461462 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726992

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.151G>T (p.A51S) alteration is located in exon 2 (coding exon 2) of the FAM105A gene. This alteration results from a G to T substitution at nucleotide position 151, causing the alanine (A) at amino acid position 51 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.6
DANN	Benign	0.91
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.010
Sift	Benign	0.51	T
Sift4G	Benign	0.43	T
Polyphen		0.037	B
Vest4		0.064
MutPred		0.28		Loss of helix (P = 0.0237);
MVP		0.20
MPC		0.17
ClinPred		0.17	T
GERP RS		3.6
Varity_R		0.027
gMVP		0.13

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-14601160;