8-23294794-C-A

Variant summary

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

The NM_001136108.3(R3HCC1):​c.1122C>A​(p.Phe374Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,551,280 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

R3HCC1
NM_001136108.3 missense

Scores

1
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110
Variant links:
Genes affected
R3HCC1 (HGNC:27329): (R3H domain and coiled-coil containing 1) Predicted to enable nucleic acid binding activity. [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=0.12144515).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
R3HCC1NM_001136108.3 linkc.1122C>A p.Phe374Leu missense_variant 7/8 ENST00000265806.12 NP_001129580.2 Q9Y3T6-1
R3HCC1NM_001301650.2 linkc.996C>A p.Phe332Leu missense_variant 8/9 NP_001288579.1 Q9Y3T6-3
R3HCC1NR_125897.1 linkn.1091C>A non_coding_transcript_exon_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
R3HCC1ENST00000265806.12 linkc.1122C>A p.Phe374Leu missense_variant 7/81 NM_001136108.3 ENSP00000265806.8 Q9Y3T6-1A0A0R4J2E2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152122
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000257
AC:
4
AN:
155804
Hom.:
0
AF XY:
0.0000242
AC XY:
2
AN XY:
82622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000663
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
22
AN:
1399158
Hom.:
0
Cov.:
30
AF XY:
0.0000145
AC XY:
10
AN XY:
690080
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000204
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152122
Hom.:
1
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.0000400
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 21, 2022The c.561C>A (p.F187L) alteration is located in exon 7 (coding exon 4) of the R3HCC1 gene. This alteration results from a C to A substitution at nucleotide position 561, causing the phenylalanine (F) at amino acid position 187 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
Pathogenic
0.86
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;.;.;.
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.75
T;T;.;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-3.7
.;.;D;D
REVEL
Benign
0.17
Sift
Benign
0.17
.;.;T;T
Sift4G
Benign
0.22
T;T;T;T
Vest4
0.26
MutPred
0.40
.;.;Gain of MoRF binding (P = 0.1209);.;
MVP
0.067
ClinPred
0.77
D
GERP RS
3.0
gMVP
0.44

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: rs764981644; hg19: chr8-23152307; API