chr12-50360780-T-G

Variant names:

• chr12-50360780-T-G
• rs12303082
• NM_001145475.3:c.559A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145475.3(FAM186A):​c.559A>C​(p.Lys187Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,534,630 control chromosomes in the GnomAD database, including 329,259 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31488 hom., cov: 32)
  • Exomes 𝑓: 0.65 (297771 hom.)
• Consequence: FAM186A NM_001145475.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.20
• Publications: 38 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8962045E-6).
• BP6: Variant 12-50360780-T-G is Benign according to our data. Variant chr12-50360780-T-G is described in ClinVar as [Benign]. Clinvar id is 1278322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.559A>C	p.Lys187Gln	missense_variant	Exon 3 of 8	ENST00000327337.6	NP_001138947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM186A	ENST00000327337.6	c.559A>C	p.Lys187Gln	missense_variant	Exon 3 of 8	5	NM_001145475.3	ENSP00000329995.5
FAM186A	ENST00000543111.5	c.559A>C	p.Lys187Gln	missense_variant	Exon 3 of 8	5		ENSP00000441337.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96788 AN: 151800 Hom.: 31453 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.627

GnomAD2 exomes AF: 0.672 AC: 94656 AN: 140946 AF XY: 0.660

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.784

Gnomad ASJ exome AF: 0.708

Gnomad EAS exome AF: 0.748

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.653 AC: 903445 AN: 1382710 Hom.: 297771 Cov.: 38 AF XY: 0.650 AC XY: 442416 AN XY: 681044

African (AFR) AF: 0.525 AC: 16121 AN: 30722

American (AMR) AF: 0.771 AC: 24943 AN: 32360

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 17416 AN: 24752

East Asian (EAS) AF: 0.754 AC: 26675 AN: 35392

South Asian (SAS) AF: 0.521 AC: 38948 AN: 74790

European-Finnish (FIN) AF: 0.740 AC: 36298 AN: 49066

Middle Eastern (MID) AF: 0.598 AC: 3367 AN: 5630

European-Non Finnish (NFE) AF: 0.655 AC: 702974 AN: 1072602

Other (OTH) AF: 0.639 AC: 36703 AN: 57396

GnomAD4 genome AF: 0.638 AC: 96880 AN: 151920 Hom.: 31488 Cov.: 32 AF XY: 0.643 AC XY: 47773 AN XY: 74262

African (AFR) AF: 0.534 AC: 22104 AN: 41422

American (AMR) AF: 0.730 AC: 11138 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2431 AN: 3466

East Asian (EAS) AF: 0.739 AC: 3820 AN: 5166

South Asian (SAS) AF: 0.509 AC: 2446 AN: 4808

European-Finnish (FIN) AF: 0.750 AC: 7909 AN: 10552

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44816 AN: 67938

Other (OTH) AF: 0.628 AC: 1324 AN: 2108

Alfa AF: 0.654 Hom.: 109144

Bravo AF: 0.636

TwinsUK AF: 0.641 AC: 2375

ALSPAC AF: 0.645 AC: 2487

ExAC AF: 0.587 AC: 12416

Asia WGS AF: 0.609 AC: 2116 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29547645, 26553438) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.0045	.;T
Eigen	Benign	-0.074
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.49	T;T
MetaRNN	Benign	0.0000019	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.32	.;N
PhyloP100		3.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.12
Sift	Benign	0.25	T;T
Sift4G	Uncertain	0.037	D;D
Polyphen		0.99	.;D
Vest4		0.067
ClinPred		0.037	T
GERP RS		4.7
Varity_R		0.13
gMVP		0.0097
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12303082; hg19: chr12-50754563; COSMIC: COSV59245845; COSMIC: COSV59245845;