dbSNP rs760921646: FAM186B:p.Pro787Ala (chr12-49598760-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032130.3(FAM186B):c.2359C>G(p.Pro787Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,606,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

FAM186B
NM_032130.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

2 publications found

Variant links:

Genes affected

FAM186B (HGNC:25296): (family with sequence similarity 186 member B) This gene product is a member of the FAM186 family, however, its exact function is not known. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

FAM186B links:

PRPF40B (HGNC:25031): (pre-mRNA processing factor 40 homolog B) This gene encodes a WW-domain containing protein similar to yeast splicing factor PRP40. This protein has been shown to interact with Huntingtin and methyl CpG binding protein 2 (MeCP2). Alternative splicing results in different transcript variants. [provided by RefSeq, Aug 2014]

PRPF40B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11169118).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032130.3. 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
	FAM186B	NM_032130.3	MANE Select	c.2359C>G	p.Pro787Ala	missense	Exon 5 of 7	NP_115506.1	Q8IYM0-1
	FAM186B	NR_027450.2		n.2701C>G		non_coding_transcript_exon	Exon 5 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM186B	ENST00000257894.2	TSL:1 MANE Select	c.2359C>G	p.Pro787Ala	missense	Exon 5 of 7	ENSP00000257894.2	Q8IYM0-1
FAM186B	ENST00000532262.5	TSL:1	c.1198C>G	p.Pro400Ala	missense	Exon 2 of 5	ENSP00000436995.1	A0A0C4DGG0
FAM186B	ENST00000548841.5	TSL:5	c.28C>G	p.Pro10Ala	missense	Exon 1 of 4	ENSP00000448989.1	H0YIB0

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000538

AC:

AN:

241516

AF XY:

0.00000763

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000714

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1455032

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

723858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.0000226

AC:

AN:

44310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.000605

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

85714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4852

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110382

Other (OTH)

AF:

0.00

AC:

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151086

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41016

American (AMR)

AF:

0.00

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000197

AC:

AN:

5076

South Asian (SAS)

AF:

0.00

AC:

AN:

4688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67830

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.80

M_CAP

Benign

0.013

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.1

PhyloP100

1.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

REVEL

Benign

0.19

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.62

MutPred

0.39

Gain of helix (P = 0.005)

MVP

0.50

MPC

0.58

ClinPred

0.26

GERP RS

3.3

PromoterAI

0.074

Neutral

(source)

Varity_R

0.15

gMVP

0.086

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over