X-37008439-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001013736.3(FAM47C):​c.29C>T​(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,208,028 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.000025 ( 0 hom. 12 hem. )

Consequence

FAM47C
NM_001013736.3 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.446
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06768513).
BS2
High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM47CNM_001013736.3 linkc.29C>T p.Pro10Leu missense_variant Exon 1 of 1 ENST00000358047.5 NP_001013758.1 Q5HY64

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM47CENST00000358047.5 linkc.29C>T p.Pro10Leu missense_variant Exon 1 of 1 6 NM_001013736.3 ENSP00000367913.3 Q5HY64

Frequencies

GnomAD3 genomes
AF:
0.0000176
AC:
2
AN:
113410
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
35540
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:
0.0000375
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000112
AC:
2
AN:
178214
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
63472
show subpopulations
Gnomad AFR exome
AF:
0.0000792
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000127
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000247
AC:
27
AN:
1094618
Hom.:
0
Cov.:
34
AF XY:
0.0000333
AC XY:
12
AN XY:
360522
show subpopulations
Gnomad4 AFR exome
AF:
0.0000761
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000332
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000238
Gnomad4 OTH exome
AF:
0.0000436
GnomAD4 genome
AF:
0.0000176
AC:
2
AN:
113410
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
35540
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000375
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.29C>T (p.P10L) alteration is located in exon 1 (coding exon 1) of the FAM47C gene. This alteration results from a C to T substitution at nucleotide position 29, causing the proline (P) at amino acid position 10 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.28
DANN
Benign
0.94
DEOGEN2
Benign
0.020
T
FATHMM_MKL
Benign
0.0077
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.068
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-4.0
D
REVEL
Benign
0.014
Sift
Benign
0.31
T
Sift4G
Benign
0.58
T
Polyphen
0.062
B
Vest4
0.066
MutPred
0.10
Loss of glycosylation at P10 (P = 0.0528);
MVP
0.048
MPC
0.25
ClinPred
0.064
T
GERP RS
0.75
Varity_R
0.093
gMVP
0.047

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781862715; hg19: chrX-37026512; API