Genetic Variant NM_021806.4:c.362G>A (chrX-154507834-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021806.4(FAM3A):c.362G>A(p.Arg121Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,192,819 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000026 ( 0 hom. 11 hem. )

Consequence

FAM3A
NM_021806.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.816

Publications

1 publications found

Variant links:

Genes affected

FAM3A (HGNC:13749): (FAM3 metabolism regulating signaling molecule A) This gene encodes a cytokine-like protein. The expression of this gene may be regulated by peroxisome proliferator-activated receptor gamma, and the encoded protein may be involved in the regulation of glucose and lipid metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

FAM3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02620539).

BP6

Variant X-154507834-C-T is Benign according to our data. Variant chrX-154507834-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661849.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021806.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM3A	NM_021806.4	MANE Select	c.362G>A	p.Arg121Gln	missense	Exon 6 of 9	NP_068578.2	P98173-1
FAM3A	NM_001282311.2		c.404G>A	p.Arg135Gln	missense	Exon 7 of 10	NP_001269240.1	D3DWX8
FAM3A	NM_001363822.2		c.383G>A	p.Arg128Gln	missense	Exon 7 of 10	NP_001350751.1	Q5HY75

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM3A	ENST00000447601.7	TSL:1 MANE Select	c.362G>A	p.Arg121Gln	missense	Exon 6 of 9	ENSP00000416146.2	P98173-1
FAM3A	ENST00000858761.1		c.452G>A	p.Arg151Gln	missense	Exon 6 of 9	ENSP00000528820.1
FAM3A	ENST00000858759.1		c.410G>A	p.Arg137Gln	missense	Exon 6 of 9	ENSP00000528818.1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00113

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

GnomAD2 exomes

AF:

0.0000822

AC:

AN:

145950

AF XY:

0.0000887

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000912

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000772

Gnomad NFE exome

AF:

0.0000327

Gnomad OTH exome

AF:

0.000266

GnomAD4 exome

AF:

0.0000259

AC:

AN:

1080145

Hom.:

Cov.:

AF XY:

0.0000313

AC XY:

AN XY:

351877

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26125

American (AMR)

AF:

0.00

AC:

AN:

32931

Ashkenazi Jewish (ASJ)

AF:

0.000689

AC:

AN:

18862

East Asian (EAS)

AF:

0.00

AC:

AN:

29503

South Asian (SAS)

AF:

0.0000969

AC:

AN:

51585

European-Finnish (FIN)

AF:

0.0000522

AC:

AN:

38295

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3903

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

833566

Other (OTH)

AF:

0.000110

AC:

AN:

45375

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000266

AC:

AN:

112674

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

34824

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31056

American (AMR)

AF:

0.00

AC:

AN:

10739

Ashkenazi Jewish (ASJ)

AF:

0.00113

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3574

South Asian (SAS)

AF:

0.00

AC:

AN:

2769

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6255

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53180

Other (OTH)

AF:

0.00

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

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:

0.000217

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000673

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.026

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.23

PhyloP100

0.82

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.070

REVEL

Benign

0.0060

Sift

Benign

0.30

Sift4G

Benign

0.49

Polyphen

0.034

Vest4

0.39

MutPred

0.31

Gain of catalytic residue at M125 (P = 0.0245)

MVP

0.48

MPC

0.34

ClinPred

0.077

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.058

gMVP

0.70

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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