chr12-50350970-T-G

Variant names:

• chr12-50350970-T-G
• rs10506292
• NM_001145475.3:c.5862A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145475.3(FAM186A):​c.5862A>C​(p.Lys1954Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM186A NM_001145475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16271743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.5862A>C	p.Lys1954Asn	missense_variant	Exon 4 of 8	ENST00000327337.6	NP_001138947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM186A	ENST00000327337.6	c.5862A>C	p.Lys1954Asn	missense_variant	Exon 4 of 8	5	NM_001145475.3	ENSP00000329995.5
FAM186A	ENST00000543111.5	c.5862A>C	p.Lys1954Asn	missense_variant	Exon 4 of 8	5		ENSP00000441337.1
FAM186A	ENST00000543096.5	c.-106A>C		upstream_gene_variant		2		ENSP00000443703.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399268 Hom.: 0 Cov.: 72 AF XY: 0.00000145 AC XY: 1 AN XY: 690138

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078938

Other (OTH) AF: 0.00 AC: 0 AN: 57994

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L
PhyloP100		0.45
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.085
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;D
Vest4		0.033
MutPred		0.32		Loss of methylation at K1954 (P = 0.0219);Loss of methylation at K1954 (P = 0.0219);
MVP		0.030
ClinPred		0.44	T
GERP RS		2.7
PromoterAI		-0.0012	Neutral
Varity_R		0.13
gMVP		0.034
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs10506292; hg19: chr12-50744753;