12-50350970-T-C

Position:

• chr12-50350970-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001145475.3(FAM186A):​c.5862A>G​(p.Lys1954Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,551,106 control chromosomes in the GnomAD database, including 332,723 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31525 hom., cov: 31)
  • Exomes 𝑓: 0.65 (301198 hom.)
• Consequence: FAM186A NM_001145475.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.45 with no splicing effect.
• 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/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.5862A>G	p.Lys1954Lys	synonymous_variant	4/8	ENST00000327337.6	NP_001138947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM186A	ENST00000327337.6	c.5862A>G	p.Lys1954Lys	synonymous_variant	4/8	5	NM_001145475.3	ENSP00000329995.5
FAM186A	ENST00000543111.5	c.5862A>G	p.Lys1954Lys	synonymous_variant	4/8	5		ENSP00000441337.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96847 AN: 151844 Hom.: 31490 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.628

GnomAD3 exomes AF: 0.670 AC: 102964 AN: 153622 Hom.: 35263 AF XY: 0.656 AC XY: 53484 AN XY: 81518

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.783

Gnomad ASJ exome AF: 0.705

Gnomad EAS exome AF: 0.748

Gnomad SAS exome AF: 0.516

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.663

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.653 AC: 914173 AN: 1399144 Hom.: 301198 Cov.: 72 AF XY: 0.649 AC XY: 448062 AN XY: 690086

Gnomad4 AFR exome AF: 0.525

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.703

Gnomad4 EAS exome AF: 0.754

Gnomad4 SAS exome AF: 0.522

Gnomad4 FIN exome AF: 0.740

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.638 AC: 96939 AN: 151962 Hom.: 31525 Cov.: 31 AF XY: 0.643 AC XY: 47799 AN XY: 74280

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.629

Alfa AF: 0.661 Hom.: 31990

Bravo AF: 0.636

Asia WGS AF: 0.609 AC: 2115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs10506292; hg19: chr12-50744753; COSMIC: COSV59247200; COSMIC: COSV59247200;