Genetic Variant FAM47C:p.Pro6Gln (chrX-37008427-C-A) – 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.17C>A(p.Pro6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,203,306 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.0000028 ( 0 hom. 2 hem. )

Consequence

FAM47C
NM_001013736.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.934

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=0.14718378).

BS2

High Hemizygotes in GnomAdExome4 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.17C>A	p.Pro6Gln	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.17C>A	p.Pro6Gln	missense	Exon 1 of 1	ENSP00000367913.3	Q5HY64

Frequencies

GnomAD3 genomes

AF:

0.00000883

AC:

AN:

113298

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1090008

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

357026

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26198

American (AMR)

AF:

0.00

AC:

AN:

34790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19202

East Asian (EAS)

AF:

0.00

AC:

AN:

29970

South Asian (SAS)

AF:

0.00

AC:

AN:

53538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40265

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4045

European-Non Finnish (NFE)

AF:

0.00000359

AC:

AN:

836364

Other (OTH)

AF:

0.00

AC:

AN:

45636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00000883

AC:

AN:

113298

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

35430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31230

American (AMR)

AF:

0.00

AC:

AN:

10859

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3556

South Asian (SAS)

AF:

0.00

AC:

AN:

2823

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

53394

Other (OTH)

AF:

0.00

AC:

AN:

1536

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.4

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.45

M_CAP

Benign

0.0010

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

-0.93

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.024

Sift

Benign

0.041

Sift4G

Benign

0.16

Polyphen

0.99

Vest4

0.11

MutPred

0.11

Loss of glycosylation at S11 (P = 0.1724)

MVP

0.061

MPC

0.66

ClinPred

0.39

GERP RS

-0.92

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.17

gMVP

0.042

Mutation Taster

=100/0

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over