Genetic Variant NM_203408.4:c.1726C>G (chrX-34130553-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_203408.4(FAM47A):c.1726C>G(p.Arg576Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,209,657 control chromosomes in the GnomAD database, including 31 homozygotes. There are 579 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0098 ( 9 hom., 270 hem., cov: 22)

Exomes 𝑓: 0.0012 ( 22 hom. 309 hem. )

Consequence

FAM47A
NM_203408.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.646

Publications

2 publications found

Variant links:

Genes affected

FAM47A (HGNC:29962): (family with sequence similarity 47 member A)

FAM47A links:

ENSG00000233928 (HGNC:):

ENSG00000233928 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003322959).

BP6

Variant X-34130553-G-C is Benign according to our data. Variant chrX-34130553-G-C is described in ClinVar as Benign. ClinVar VariationId is 3038371.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00985 (1097/111421) while in subpopulation AFR AF = 0.034 (1044/30671). AF 95% confidence interval is 0.0323. There are 9 homozygotes in GnomAd4. There are 270 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203408.4. 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
	FAM47A	NM_203408.4	MANE Select	c.1726C>G	p.Arg576Gly	missense	Exon 1 of 1	NP_981953.2	Q5JRC9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM47A	ENST00000346193.5	TSL:6 MANE Select	c.1726C>G	p.Arg576Gly	missense	Exon 1 of 1	ENSP00000345029.3	Q5JRC9
ENSG00000233928	ENST00000653446.1		n.390+53984G>C		intron	N/A
ENSG00000233928	ENST00000656777.1		n.452+53984G>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00978

AC:

1089

AN:

111366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00401

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000384

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00469

GnomAD2 exomes

AF:

0.00265

AC:

482

AN:

182189

AF XY:

0.00172

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000858

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00117

AC:

1280

AN:

1098236

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

309

AN XY:

363592

show subpopulations

African (AFR)

AF:

0.0395

AC:

1044

AN:

26403

American (AMR)

AF:

0.00159

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.0000739

AC:

AN:

54145

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40526

Middle Eastern (MID)

AF:

0.000967

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000416

AC:

AN:

842134

Other (OTH)

AF:

0.00297

AC:

137

AN:

46097

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00985

AC:

1097

AN:

111421

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

270

AN XY:

33623

show subpopulations

African (AFR)

AF:

0.0340

AC:

1044

AN:

30671

American (AMR)

AF:

0.00400

AC:

AN:

10495

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.000386

AC:

AN:

2594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53078

Other (OTH)

AF:

0.00462

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

128

171

214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00146

Hom.:

Bravo

AF:

0.0113

ESP6500AA

AF:

0.0283

AC:

106

ESP6500EA

AF:

0.000150

AC:

ExAC

AF:

0.00319

AC:

387

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

FAM47A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.96

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.51

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.0015

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

PhyloP100

-0.65

PrimateAI

Benign

0.31

PROVEAN

Benign

0.050

REVEL

Benign

0.0090

Sift

Benign

0.56

Sift4G

Benign

0.42

Polyphen

0.0040

Vest4

0.053

MVP

0.043

MPC

0.25

ClinPred

0.0023

GERP RS

-1.0

Varity_R

0.056

gMVP

0.078

Mutation Taster

=100/0

polymorphism (auto)

(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