Genetic Variant FAM76B:p.Met298Ile (chr11-95775958-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_144664.5(FAM76B):c.894G>C(p.Met298Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000565 in 1,592,896 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

FAM76B
NM_144664.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31

Publications

0 publications found

Variant links:

Genes affected

FAM76B (HGNC:28492): (family with sequence similarity 76 member B) Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

FAM76B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41109037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144664.5. 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
	FAM76B	NM_144664.5	MANE Select	c.894G>C	p.Met298Ile	missense	Exon 9 of 10	NP_653265.3
	FAM76B	NM_001330357.2		c.891G>C	p.Met297Ile	missense	Exon 9 of 10	NP_001317286.1	F5GX09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM76B	ENST00000358780.10	TSL:1 MANE Select	c.894G>C	p.Met298Ile	missense	Exon 9 of 10	ENSP00000351631.5	Q5HYJ3-1
FAM76B	ENST00000398187.6	TSL:1	n.*250G>C		non_coding_transcript_exon	Exon 10 of 11	ENSP00000381248.2	Q5HYJ3-3
FAM76B	ENST00000543641.5	TSL:1	n.*250G>C		non_coding_transcript_exon	Exon 10 of 12	ENSP00000444087.1	Q5HYJ3-3

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1441602

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717226

show subpopulations

African (AFR)

AF:

0.0000621

AC:

AN:

32208

American (AMR)

AF:

0.00

AC:

AN:

42216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25436

East Asian (EAS)

AF:

0.00

AC:

AN:

38790

South Asian (SAS)

AF:

0.00

AC:

AN:

83262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1101908

Other (OTH)

AF:

0.0000169

AC:

AN:

59300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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:

0.0000330

AC:

AN:

151294

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73906

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41298

American (AMR)

AF:

0.00

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67486

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000151

ClinVar

ClinVar submissions

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

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0061

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

PhyloP100

7.3

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.57

Polyphen

0.84

Vest4

0.62

MutPred

0.28

Loss of ubiquitination at K294 (P = 0.0561)

MVP

0.52

MPC

0.43

ClinPred

0.67

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.23

Mutation Taster

=33/67

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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