12-50330655-C-G

Variant names:

• chr12-50330655-C-G
• rs1348948063
• NM_001145475.3:c.6952G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145475.3(FAM186A):​c.6952G>C​(p.Gly2318Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,200 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2318C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FAM186A NM_001145475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.6952G>C	p.Gly2318Arg	missense_variant	Exon 7 of 8	ENST00000327337.6	NP_001138947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM186A	ENST00000327337.6	c.6952G>C	p.Gly2318Arg	missense_variant	Exon 7 of 8	5	NM_001145475.3	ENSP00000329995.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398200 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.024	.;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-7.6	D;D;D
REVEL	Benign	0.22
Sift	Benign	0.088	T;D;D
Sift4G	Benign	0.073	T;D;D
Polyphen		1.0	.;D;D
Vest4		0.76
MutPred		0.58		.;Gain of MoRF binding (P = 0.0737);Gain of MoRF binding (P = 0.0737);
MVP		0.49
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.41
gMVP		0.029

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

Publications

LitVar

Other links and lift over

dbSNP: rs1348948063; hg19: chr12-50724438;