Genetic Variant FAM72B:p.Gly29Arg (chr1-121183405-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001100910.2(FAM72B):c.85G>A(p.Gly29Arg) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 13)

Exomes 𝑓: 0.000024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM72B
NM_001100910.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.99

Publications

0 publications found

Variant links:

Genes affected

FAM72B (HGNC:24805): (family with sequence similarity 72 member B) Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

FAM72B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.847

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100910.2. 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
	FAM72B	NM_001100910.2	MANE Select	c.85G>A	p.Gly29Arg	missense	Exon 1 of 4	NP_001094380.1	Q86X60-1
	FAM72B	NM_001320149.2		c.32+53G>A		intron	N/A	NP_001307078.1	Q86X60-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM72B	ENST00000369390.7	TSL:1 MANE Select	c.85G>A	p.Gly29Arg	missense	Exon 1 of 4	ENSP00000358397.3	Q86X60-1
FAM72B	ENST00000619376.4	TSL:1	c.85G>A	p.Gly29Arg	missense	Exon 1 of 3	ENSP00000482799.1	A0A087WZP4
FAM72B	ENST00000355228.8	TSL:1	c.32+53G>A		intron	N/A	ENSP00000347368.4	Q86X60-2

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110826

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000363

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000238

AC:

AN:

1427076

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

708980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32338

American (AMR)

AF:

0.00

AC:

AN:

42424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25210

East Asian (EAS)

AF:

0.00

AC:

AN:

39346

South Asian (SAS)

AF:

0.00

AC:

AN:

84276

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52850

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4014

European-Non Finnish (NFE)

AF:

0.0000285

AC:

AN:

1087788

Other (OTH)

AF:

0.0000510

AC:

AN:

58830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000180

AC:

AN:

110826

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

52154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27570

American (AMR)

AF:

0.00

AC:

AN:

10148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2978

East Asian (EAS)

AF:

0.00

AC:

AN:

3698

South Asian (SAS)

AF:

0.00

AC:

AN:

2630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0000363

AC:

AN:

55090

Other (OTH)

AF:

0.00

AC:

AN:

1386

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

Alfa

AF:

0.00

Hom.:

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

0.99

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.66

PhyloP100

7.0

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.8

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Vest4

0.91

MutPred

0.57

Loss of sheet (P = 0.0037)

MVP

0.51

ClinPred

0.99

GERP RS

3.8

gMVP

0.69

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over