12-50333944-C-A

Variant names:

• chr12-50333944-C-A
• NM_001145475.3:c.6663G>T

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.6663G>T​(p.Gln2221His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM186A NM_001145475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.774
• 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=0.10957196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM186A	NM_001145475.3	MANE Select	c.6663G>T	p.Gln2221His	missense	Exon 5 of 8	NP_001138947.1	A6NE01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM186A	ENST00000327337.6	TSL:5 MANE Select	c.6663G>T	p.Gln2221His	missense	Exon 5 of 8	ENSP00000329995.5	A6NE01
	FAM186A	ENST00000543111.5	TSL:5	c.6663G>T	p.Gln2221His	missense	Exon 5 of 8	ENSP00000441337.1	F5GYN0
	FAM186A	ENST00000539751.1	TSL:5	n.159G>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000437706.1	H0YFA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.77
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.046
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.34	B
Vest4		0.091
MutPred		0.21		Loss of methylation at K2224 (P = 0.0877)
MVP		0.061
ClinPred		0.62	D
GERP RS		-0.70
Varity_R		0.20
gMVP		0.025
Mutation Taster		=100/0	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

hg19: chr12-50727727;