12-50334028-C-A

Position:

• chr12-50334028-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145475.3(FAM186A):​c.6579G>T​(p.Met2193Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM186A NM_001145475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30282792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.6579G>T	p.Met2193Ile	missense_variant	5/8	ENST00000327337.6	NP_001138947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM186A	ENST00000327337.6	c.6579G>T	p.Met2193Ile	missense_variant	5/8	5	NM_001145475.3	ENSP00000329995.5
FAM186A	ENST00000543111.5	c.6579G>T	p.Met2193Ile	missense_variant	5/8	5		ENSP00000441337.1
FAM186A	ENST00000543096.5	c.612G>T	p.Met204Ile	missense_variant	2/5	2		ENSP00000443703.1
FAM186A	ENST00000539751.1	n.75G>T		non_coding_transcript_exon_variant	1/3	5		ENSP00000437706.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	.;.;T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.019
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.81	.;.;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D;N;N
REVEL	Benign	0.16
Sift	Benign	0.031	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0, 0.98	.;D;D
Vest4		0.17
MutPred		0.12		.;Loss of disorder (P = 0.0736);Loss of disorder (P = 0.0736);
MVP		0.072
ClinPred		0.82	D
GERP RS		3.5
Varity_R		0.26
gMVP		0.075

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: rs6580742; hg19: chr12-50727811;