chr12-50334077-G-T

Position:

• chr12-50334077-G-T

Variant summary

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

The NM_001145475.3(FAM186A):​c.6530C>A​(p.Ala2177Asp) 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. 14/20 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: 32)
• Consequence: FAM186A NM_001145475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214

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=0.37376696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM186A	NM_001145475.3	c.6530C>A	p.Ala2177Asp	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.6530C>A	p.Ala2177Asp	missense_variant	5/8	5	NM_001145475.3	ENSP00000329995.5
FAM186A	ENST00000543111.5	c.6530C>A	p.Ala2177Asp	missense_variant	5/8	5		ENSP00000441337.1
FAM186A	ENST00000543096.5	c.563C>A	p.Ala188Asp	missense_variant	2/5	2		ENSP00000443703.1
FAM186A	ENST00000539751.1	n.26C>A		non_coding_transcript_exon_variant	1/3	5		ENSP00000437706.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.6530C>A (p.A2177D) alteration is located in exon 5 (coding exon 5) of the FAM186A gene. This alteration results from a C to A substitution at nucleotide position 6530, causing the alanine (A) at amino acid position 2177 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;.;L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Benign	0.087
Sift	Benign	0.17	T;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.85	.;P;P
Vest4		0.61
MutPred		0.34		.;Gain of disorder (P = 0.0526);Gain of disorder (P = 0.0526);
MVP		0.42
ClinPred		0.72	D
GERP RS		1.5
Varity_R		0.27
gMVP		0.063

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50727860;