Variant 12-50396303-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145475.3(FAM186A):c.182G>A(p.Arg61Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000976 in 1,536,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FAM186A
NM_001145475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

FAM186A (HGNC:26980): (family with sequence similarity 186 member A)

FAM186A links:

LARP4 (HGNC:24320): (La ribonucleoprotein 4) Enables mRNA 3'-UTR binding activity and poly(A) binding activity. Involved in cytoskeleton organization; positive regulation of translation; and regulation of cell morphogenesis. Located in cytosol. Colocalizes with cytoplasmic stress granule; cytosolic small ribosomal subunit; and polysome. [provided by Alliance of Genome Resources, Apr 2022]

LARP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3 linkuse as main transcript	c.182G>A	p.Arg61Gln	missense_variant	1/8	ENST00000327337.6	NP_001138947.1	A6NE01

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAM186A	ENST00000327337.6 linkuse as main transcript	c.182G>A	p.Arg61Gln	missense_variant	1/8	5	NM_001145475.3	ENSP00000329995.5	A6NE01
FAM186A	ENST00000543111.5 linkuse as main transcript	c.182G>A	p.Arg61Gln	missense_variant	1/8	5		ENSP00000441337.1	F5GYN0
LARP4	ENST00000550522.5 linkuse as main transcript	c.-193+3715C>T		intron_variant		4		ENSP00000448180.1	F8VSA9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000701

AC:

AN:

142668

Hom.:

AF XY:

0.00

AC XY:

AN XY:

75112

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000460

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000101

AC:

AN:

1384204

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

681176

show subpopulations

Gnomad4 AFR exome

AF:

0.0000642

Gnomad4 AMR exome

AF:

0.0000305

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000653

Gnomad4 OTH exome

AF:

0.0000522

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000279

Hom.:

Bravo

AF:

0.00000378

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

Mar 15, 2024

The c.182G>A (p.R61Q) alteration is located in exon 1 (coding exon 1) of the FAM186A gene. This alteration results from a G to A substitution at nucleotide position 182, causing the arginine (R) at amino acid position 61 to be replaced by a glutamine (Q). 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

Uncertain

0.38

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.083

.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

.;M

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.49

MutPred

0.31

Loss of MoRF binding (P = 0.0523);Loss of MoRF binding (P = 0.0523);

MVP

0.24

ClinPred

0.95

GERP RS

4.6

Varity_R

0.39

gMVP

0.041

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

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