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GeneBe

10-16752545-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM2_Supporting

The NM_012425.4(RSU1):c.592G>C(p.Glu198Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152182 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

RSU1
NM_012425.4 missense

Scores

5
4
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.54

Links

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, gnomad allele frequency = 0.00000657 (1/152182) while in subpopulation NFE AF= 0.0000147 (1/68036). AF 95% confidence interval is 0. There are 0 homozygotes in gnomad. There are 1 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RSU1NM_012425.4 linkuse as main transcriptc.592G>C p.Glu198Gln missense_variant 7/9 ENST00000345264.10
RSU1NM_152724.3 linkuse as main transcriptc.433G>C p.Glu145Gln missense_variant 6/8
RSU1XM_047425617.1 linkuse as main transcriptc.592G>C p.Glu198Gln missense_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RSU1ENST00000345264.10 linkuse as main transcriptc.592G>C p.Glu198Gln missense_variant 7/91 NM_012425.4 P1Q15404-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152182
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460800
Hom.:
0
AF XY:
0.00000550
AC XY:
4
AN XY:
726832
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 26, 2022The c.592G>C (p.E198Q) alteration is located in exon 7 (coding exon 6) of the RSU1 gene. This alteration results from a G to C substitution at nucleotide position 592, causing the glutamic acid (E) at amino acid position 198 to be replaced by a glutamine (Q). 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
0.62
BayesDel_addAF
Benign
0.0016
T
BayesDel_noAF
Benign
-0.24
Cadd
Pathogenic
26
Dann
Uncertain
1.0
DEOGEN2
Benign
0.22
T;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.64
D;D;D
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.9
M;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.5
D;D;.
REVEL
Benign
0.18
Sift
Uncertain
0.0070
D;D;.
Sift4G
Benign
0.087
T;T;.
Polyphen
0.98
D;D;.
Vest4
0.67
MVP
0.41
MPC
0.99
ClinPred
0.89
D
GERP RS
5.3
Varity_R
0.40
gMVP
0.64

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: rs200140782; hg19: chr10-16794544; API