12-31981347-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018169.4(RESF1):​c.392A>T​(p.His131Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,038 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

RESF1
NM_018169.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.249
Variant links:
Genes affected
RESF1 (HGNC:25559): (retroelement silencing factor 1) Predicted to enable histone binding activity and histone methyltransferase binding activity. Predicted to be involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate and positive regulation of DNA methylation-dependent heterochromatin assembly. Predicted to act upstream of or within response to bacterium. Predicted to be located in nucleus. Predicted to colocalize with gamma-tubulin complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07838991).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RESF1NM_018169.4 linkc.392A>T p.His131Leu missense_variant Exon 4 of 6 ENST00000312561.9 NP_060639.4 Q9HCM1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RESF1ENST00000312561.9 linkc.392A>T p.His131Leu missense_variant Exon 4 of 6 1 NM_018169.4 ENSP00000310338.4 Q9HCM1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
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
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461804
Hom.:
0
Cov.:
44
AF XY:
0.00000550
AC XY:
4
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.392A>T (p.H131L) alteration is located in exon 4 (coding exon 1) of the KIAA1551 gene. This alteration results from a A to T substitution at nucleotide position 392, causing the histidine (H) at amino acid position 131 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
0.10
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
14
DANN
Benign
0.65
DEOGEN2
Benign
0.076
T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.099
N
LIST_S2
Benign
0.37
T;T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.078
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.5
L;.
PrimateAI
Benign
0.25
T
PROVEAN
Pathogenic
-4.6
D;D
REVEL
Benign
0.16
Sift
Benign
0.11
T;T
Sift4G
Uncertain
0.026
D;D
Polyphen
0.0030
B;.
Vest4
0.44
MutPred
0.46
Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP
0.099
MPC
0.012
ClinPred
0.059
T
GERP RS
-1.8
Varity_R
0.080
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs371644477; hg19: chr12-32134281; API