4-76256417-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136570.3(FAM47E):​c.314C>T​(p.Ser105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,552,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FAM47E
NM_001136570.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.720
Variant links:
Genes affected
FAM47E (HGNC:34343): (family with sequence similarity 47 member E) Enables enzyme activator activity. Involved in positive regulation of histone methylation and protein localization to chromatin. Located in chromatin; cytoplasm; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
FAM47E-STBD1 (HGNC:44667): (FAM47E-STBD1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring FAM47E (family with sequence similarity 47, member E) and STBD1 (starch binding domain 1) genes on chromosome 4. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Jul 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.024373561).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM47ENM_001136570.3 linkc.314C>T p.Ser105Leu missense_variant Exon 2 of 8 ENST00000424749.7 NP_001130042.1 Q6ZV65-3
FAM47E-STBD1NM_001242939.2 linkc.314C>T p.Ser105Leu missense_variant Exon 2 of 7 NP_001229868.1 Q6ZV65-1
FAM47ENM_001242936.1 linkc.82-7287C>T intron_variant Intron 2 of 7 NP_001229865.1 Q6ZV65-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM47EENST00000424749.7 linkc.314C>T p.Ser105Leu missense_variant Exon 2 of 8 5 NM_001136570.3 ENSP00000409423.2 Q6ZV65-3
FAM47E-STBD1ENST00000515604.5 linkc.314C>T p.Ser105Leu missense_variant Exon 2 of 7 2 ENSP00000422067.1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152178
Hom.:
0
Cov.:
32
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:
0.00115
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000902
AC:
14
AN:
155216
Hom.:
0
AF XY:
0.0000972
AC XY:
8
AN XY:
82312
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00128
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
23
AN:
1400108
Hom.:
0
Cov.:
31
AF XY:
0.0000203
AC XY:
14
AN XY:
690616
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000531
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00115
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.314C>T (p.S105L) alteration is located in exon 2 (coding exon 2) of the FAM47E gene. This alteration results from a C to T substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 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
0.13
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
14
DANN
Benign
0.92
DEOGEN2
Benign
0.045
T;.
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.93
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.024
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;.
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.8
D;D
REVEL
Benign
0.057
Sift
Benign
0.047
D;D
Sift4G
Benign
0.68
T;T
Polyphen
0.40
B;.
Vest4
0.15
MutPred
0.29
Loss of disorder (P = 0.0256);Loss of disorder (P = 0.0256);
MVP
0.048
MPC
0.040
ClinPred
0.15
T
GERP RS
3.4
Varity_R
0.12
gMVP
0.34

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: rs1267731930; hg19: chr4-77177570; COSMIC: COSV105916957; COSMIC: COSV105916957; API