Genetic Variant FAM47C:p.Pro6Ser (chrX-37008426-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001013736.3(FAM47C):c.16C>T(p.Pro6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 113,383 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 2 hem., cov: 24)

Consequence

FAM47C
NM_001013736.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Publications

0 publications found

Variant links:

Genes affected

FAM47C (HGNC:25301): (family with sequence similarity 47 member C) This gene encodes a product belonging to a family of proteins with unknown function. The coding sequence of this family member includes several tandemly repeated regions. [provided by RefSeq, Sep 2011]

FAM47C Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: XL Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

FAM47C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12999877).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013736.3. 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
	FAM47C	NM_001013736.3	MANE Select	c.16C>T	p.Pro6Ser	missense	Exon 1 of 1	NP_001013758.1	Q5HY64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47C	ENST00000358047.5	TSL:6 MANE Select	c.16C>T	p.Pro6Ser	missense	Exon 1 of 1	ENSP00000367913.3	Q5HY64

Frequencies

GnomAD3 genomes

AF:

0.0000353

AC:

AN:

113383

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000128

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

GnomAD2 exomes

AF:

0.00000584

AC:

AN:

171166

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000828

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000353

AC:

AN:

113383

Hom.:

Cov.:

AF XY:

0.0000563

AC XY:

AN XY:

35505

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

31264

American (AMR)

AF:

0.00

AC:

AN:

10867

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2662

East Asian (EAS)

AF:

0.00

AC:

AN:

3563

South Asian (SAS)

AF:

0.00

AC:

AN:

2834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6323

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53403

Other (OTH)

AF:

0.00

AC:

AN:

1539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

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

Benign

0.12

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0094

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.44

M_CAP

Benign

0.00092

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

1.0

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.020

Sift

Uncertain

0.029

Sift4G

Benign

0.10

Polyphen

0.90

Vest4

0.053

MVP

0.076

MPC

0.59

ClinPred

0.87

GERP RS

0.46

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.18

gMVP

0.052

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over