dbSNP rs73200549: FAM43A:p.Lys249Asn (chr3-194687573-G-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153690.5(FAM43A):c.747G>T(p.Lys249Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000938 in 1,587,414 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

FAM43A
NM_153690.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.05

Publications

5 publications found

Variant links:

Genes affected

FAM43A (HGNC:26888): (family with sequence similarity 43 member A)

FAM43A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01074791).

BP6

Variant 3-194687573-G-T is Benign according to our data. Variant chr3-194687573-G-T is described in ClinVar as Benign. ClinVar VariationId is 719089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153690.5. 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
	FAM43A	NM_153690.5	MANE Select	c.747G>T	p.Lys249Asn	missense	Exon 1 of 1	NP_710157.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM43A	ENST00000329759.6	TSL:6 MANE Select	c.747G>T	p.Lys249Asn	missense	Exon 1 of 1	ENSP00000371397.1	Q8N2R8

Frequencies

GnomAD3 genomes

AF:

0.000952

AC:

145

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000964

AC:

192

AN:

199186

AF XY:

0.00100

show subpopulations

Gnomad AFR exome

AF:

0.000177

Gnomad AMR exome

AF:

0.0000329

Gnomad ASJ exome

AF:

0.00256

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.000937

AC:

1344

AN:

1435060

Hom.:

Cov.:

AF XY:

0.000919

AC XY:

654

AN XY:

711610

show subpopulations

African (AFR)

AF:

0.0000607

AC:

AN:

32962

American (AMR)

AF:

0.0000725

AC:

AN:

41378

Ashkenazi Jewish (ASJ)

AF:

0.00234

AC:

AN:

25664

East Asian (EAS)

AF:

0.0000260

AC:

AN:

38528

South Asian (SAS)

AF:

0.000121

AC:

AN:

82678

European-Finnish (FIN)

AF:

0.00292

AC:

147

AN:

50262

Middle Eastern (MID)

AF:

0.000185

AC:

AN:

5404

European-Non Finnish (NFE)

AF:

0.000976

AC:

1073

AN:

1098834

Other (OTH)

AF:

0.000792

AC:

AN:

59350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

175

262

350

437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<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:

0.000952

AC:

145

AN:

152354

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41584

American (AMR)

AF:

0.000131

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00129

AC:

AN:

68036

Other (OTH)

AF:

0.000946

AC:

AN:

2114

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

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:

0.00131

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000874

AC:

105

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.64

MutationAssessor

Benign

2.0

PhyloP100

3.0

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.26

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.037

Polyphen

0.047

Vest4

0.52

MutPred

0.37

Loss of ubiquitination at K249 (P = 0.0027)

MVP

0.41

ClinPred

0.041

GERP RS

2.3

Varity_R

0.68

gMVP

0.43

Mutation Taster

=89/11

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

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