NM_203408.4:c.1680T>C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_203408.4(FAM47A):​c.1680T>C​(p.Pro560Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,208,423 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 52 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., 25 hem., cov: 22)
Exomes 𝑓: 0.000088 ( 0 hom. 27 hem. )

Consequence

FAM47A
NM_203408.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.184
Variant links:
Genes affected
FAM47A (HGNC:29962): (family with sequence similarity 47 member A)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant X-34130599-A-G is Benign according to our data. Variant chrX-34130599-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2660253.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.184 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM47ANM_203408.4 linkc.1680T>C p.Pro560Pro synonymous_variant Exon 1 of 1 ENST00000346193.5 NP_981953.2 Q5JRC9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM47AENST00000346193.5 linkc.1680T>C p.Pro560Pro synonymous_variant Exon 1 of 1 6 NM_203408.4 ENSP00000345029.3 Q5JRC9

Frequencies

GnomAD3 genomes
AF:
0.000662
AC:
73
AN:
110193
Hom.:
0
Cov.:
22
AF XY:
0.000768
AC XY:
25
AN XY:
32567
show subpopulations
Gnomad AFR
AF:
0.00215
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000578
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:
0.0000380
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000170
AC:
31
AN:
181953
Hom.:
0
AF XY:
0.000104
AC XY:
7
AN XY:
67435
show subpopulations
Gnomad AFR exome
AF:
0.00202
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000525
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000224
GnomAD4 exome
AF:
0.0000883
AC:
97
AN:
1098179
Hom.:
0
Cov.:
31
AF XY:
0.0000743
AC XY:
27
AN XY:
363533
show subpopulations
Gnomad4 AFR exome
AF:
0.00235
Gnomad4 AMR exome
AF:
0.000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000369
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000131
Gnomad4 OTH exome
AF:
0.000239
GnomAD4 genome
AF:
0.000662
AC:
73
AN:
110244
Hom.:
0
Cov.:
22
AF XY:
0.000766
AC XY:
25
AN XY:
32628
show subpopulations
Gnomad4 AFR
AF:
0.00215
Gnomad4 AMR
AF:
0.000577
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000380
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000391
Hom.:
2
Bravo
AF:
0.000835

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

FAM47A-related disorder Benign:1
Feb 20, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Apr 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

FAM47A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
4.3
DANN
Benign
0.40

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: rs199939747; hg19: chrX-34148716; API