Variant 12-50334087-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001145475.3(FAM186A):c.6520C>T(p.Arg2174*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00911 in 1,543,834 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0085 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 99 hom. )

Consequence

FAM186A
NM_001145475.3 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.10

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-50334087-G-A is Benign according to our data. Variant chr12-50334087-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3387945.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3 linkuse as main transcript	c.6520C>T	p.Arg2174*	stop_gained	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.6520C>T	p.Arg2174*	stop_gained	5/8	5	NM_001145475.3	ENSP00000329995.5	A6NE01
FAM186A	ENST00000543111.5 linkuse as main transcript	c.6520C>T	p.Arg2174*	stop_gained	5/8	5		ENSP00000441337.1	F5GYN0
FAM186A	ENST00000543096.5 linkuse as main transcript	c.553C>T	p.Arg185*	stop_gained	2/5	2		ENSP00000443703.1	F5H8C1
FAM186A	ENST00000539751.1 linkuse as main transcript	n.16C>T		non_coding_transcript_exon_variant	1/3	5		ENSP00000437706.1	H0YFA1

Frequencies

GnomAD3 genomes

AF:

0.00851

AC:

1292

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00814

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00312

Gnomad FIN

AF:

0.0438

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00849

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.0103

AC:

1502

AN:

145504

Hom.:

AF XY:

0.00974

AC XY:

750

AN XY:

77040

show subpopulations

Gnomad AFR exome

AF:

0.00182

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00354

Gnomad FIN exome

AF:

0.0396

Gnomad NFE exome

AF:

0.00912

Gnomad OTH exome

AF:

0.00708

GnomAD4 exome

AF:

0.00917

AC:

12765

AN:

1391836

Hom.:

Cov.:

AF XY:

0.00901

AC XY:

6181

AN XY:

686244

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.00379

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.00885

Gnomad4 OTH exome

AF:

0.00902

GnomAD4 genome

AF:

0.00851

AC:

1293

AN:

151998

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

750

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.00813

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00333

Gnomad4 FIN

AF:

0.0438

Gnomad4 NFE

AF:

0.00850

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00788

Hom.:

Bravo

AF:

0.00547

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.0101

AC:

ExAC

AF:

0.00772

AC:

184

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

FAM186A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

0.0092

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Benign

0.97

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.053

Vest4

0.26

GERP RS

0.38

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