12-50330574-G-T

Variant names:

• chr12-50330574-G-T
• rs1228264180
• NM_001145475.3:c.7033C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001145475.3(FAM186A):​c.7033C>A​(p.Arg2345Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FAM186A NM_001145475.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002234
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11116907).
• BP7: Synonymous conserved (PhyloP=2.28 with no splicing effect.

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.7033C>A	p.Arg2345Arg	splice_region synonymous	Exon 7 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.7033C>A	p.Arg2345Arg	splice_region synonymous	Exon 7 of 8	ENSP00000329995.5	A6NE01
	FAM186A	ENST00000543111.5	TSL:5	c.7033C>A	p.Arg2345Ser	missense splice_region	Exon 7 of 8	ENSP00000441337.1	F5GYN0
	FAM186A	ENST00000539751.1	TSL:5	n.*146C>A		splice_region non_coding_transcript_exon	Exon 2 of 3	ENSP00000437706.1	H0YFA1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689432

African (AFR) AF: 0.00 AC: 0 AN: 31496

American (AMR) AF: 0.00 AC: 0 AN: 35430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35616

South Asian (SAS) AF: 0.00 AC: 0 AN: 78682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078460

Other (OTH) AF: 0.00 AC: 0 AN: 57990

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.95
Eigen	Benign	0.056
Eigen_PC	Benign	-0.031
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.074
Sift	Benign	0.20	T
Sift4G	Uncertain	0.017	D
Polyphen		0.016	B
Vest4		0.11
MutPred		0.38		Loss of MoRF binding (P = 6e-04)
MVP		0.085
ClinPred		0.33	T
GERP RS		3.2
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00022
dbscSNV1_RF	Benign	0.10
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: rs1228264180; hg19: chr12-50724357;