12-50327375-T-C

Position:

• chr12-50327375-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001145475.3(FAM186A):​c.*8A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,545,006 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (13 hom.)
• Consequence: FAM186A NM_001145475.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 12-50327375-T-C is Benign according to our data. Variant chr12-50327375-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.*8A>G		3_prime_UTR_variant	8/8	ENST00000327337.6	NP_001138947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM186A	ENST00000327337	c.*8A>G		3_prime_UTR_variant	8/8	5	NM_001145475.3	ENSP00000329995.5

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 543 AN: 152168 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00961

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00494

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00350 AC: 534 AN: 152462 Hom.: 5 AF XY: 0.00338 AC XY: 273 AN XY: 80842

Gnomad AFR exome AF: 0.000380

Gnomad AMR exome AF: 0.00152

Gnomad ASJ exome AF: 0.00509

Gnomad EAS exome AF: 0.0000920

Gnomad SAS exome AF: 0.00189

Gnomad FIN exome AF: 0.00825

Gnomad NFE exome AF: 0.00440

Gnomad OTH exome AF: 0.00512

GnomAD4 exome AF: 0.00344 AC: 4785 AN: 1392720 Hom.: 13 Cov.: 29 AF XY: 0.00342 AC XY: 2351 AN XY: 687288

Gnomad4 AFR exome AF: 0.000604

Gnomad4 AMR exome AF: 0.00178

Gnomad4 ASJ exome AF: 0.00593

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00151

Gnomad4 FIN exome AF: 0.00824

Gnomad4 NFE exome AF: 0.00349

Gnomad4 OTH exome AF: 0.00419

GnomAD4 genome AF: 0.00357 AC: 543 AN: 152286 Hom.: 5 Cov.: 32 AF XY: 0.00380 AC XY: 283 AN XY: 74460

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.00249

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00961

Gnomad4 NFE AF: 0.00494

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00434 Hom.: 4

Bravo AF: 0.00235

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

FAM186A: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.84

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: rs184058749; hg19: chr12-50721158;