Variant chr12-50334028-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145475.3(FAM186A):c.6579G>A(p.Met2193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,551,378 control chromosomes in the GnomAD database, including 21,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1346 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19973 hom. )

Consequence

FAM186A
NM_001145475.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.618

Variant links:

Genes affected

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

FAM186A 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=0.0019448996).

BP6

Variant 12-50334028-C-T is Benign according to our data. Variant chr12-50334028-C-T is described in ClinVar as [Benign]. Clinvar id is 1236725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3 linkuse as main transcript	c.6579G>A	p.Met2193Ile	missense_variant	5/8	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.6579G>A	p.Met2193Ile	missense_variant	5/8	5	NM_001145475.3	ENSP00000329995.5	A6NE01
FAM186A	ENST00000543111.5 linkuse as main transcript	c.6579G>A	p.Met2193Ile	missense_variant	5/8	5		ENSP00000441337.1	F5GYN0
FAM186A	ENST00000543096.5 linkuse as main transcript	c.612G>A	p.Met204Ile	missense_variant	2/5	2		ENSP00000443703.1	F5H8C1
FAM186A	ENST00000539751.1 linkuse as main transcript	n.75G>A		non_coding_transcript_exon_variant	1/3	5		ENSP00000437706.1	H0YFA1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17412

AN:

152040

Hom.:

1346

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0877

Gnomad ASJ

AF:

0.0945

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.118

AC:

18538

AN:

156442

Hom.:

1424

AF XY:

0.122

AC XY:

10151

AN XY:

82914

show subpopulations

Gnomad AFR exome

AF:

0.0283

Gnomad AMR exome

AF:

0.0715

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.000459

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.162

AC:

226920

AN:

1399220

Hom.:

19973

Cov.:

AF XY:

0.161

AC XY:

111285

AN XY:

690136

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.0751

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.000224

Gnomad4 SAS exome

AF:

0.107

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.149

GnomAD4 genome

AF:

0.114

AC:

17405

AN:

152158

Hom.:

1346

Cov.:

AF XY:

0.111

AC XY:

8259

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.0876

Gnomad4 ASJ

AF:

0.0945

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.152

Hom.:

5142

Bravo

AF:

0.106

TwinsUK

AF:

0.194

AC:

721

ALSPAC

AF:

0.191

AC:

735

ESP6500AA

AF:

0.0296

AC:

ESP6500EA

AF:

0.166

AC:

527

ExAC

AF:

0.113

AC:

2748

Asia WGS

AF:

0.0410

AC:

144

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2018	This variant is associated with the following publications: (PMID: 26553438, 29547645) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

.;.;T

Eigen

Benign

0.048

Eigen_PC

Benign

-0.019

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.60

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;.;L

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.6

D;N;N

REVEL

Benign

0.15

Sift

Benign

0.031

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0, 0.98

.;D;D

Vest4

0.17

MutPred

0.12

.;Loss of disorder (P = 0.0736);Loss of disorder (P = 0.0736);

ClinPred

0.043

GERP RS

3.5

Varity_R

0.26

gMVP

0.075

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