rs961360

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001378107.1(R3HDM1):​c.808A>G​(p.Met270Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.174 in 1,612,386 control chromosomes in the GnomAD database, including 32,766 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3955 hom., cov: 32)
Exomes 𝑓: 0.17 ( 28811 hom. )

Consequence

R3HDM1
NM_001378107.1 missense, splice_region

Scores

1
4
13
Splicing: ADA: 0.0009339
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.97

Publications

51 publications found
Variant links:
Genes affected
R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0026819408).
BP6
Variant 2-135636088-A-G is Benign according to our data. Variant chr2-135636088-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 4076126.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
R3HDM1NM_001378107.1 linkc.808A>G p.Met270Val missense_variant, splice_region_variant Exon 11 of 27 ENST00000683871.1 NP_001365036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
R3HDM1ENST00000683871.1 linkc.808A>G p.Met270Val missense_variant, splice_region_variant Exon 11 of 27 NM_001378107.1 ENSP00000506980.1 A0A804HIA8

Frequencies

GnomAD3 genomes
AF:
0.211
AC:
32005
AN:
152032
Hom.:
3937
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.203
Gnomad AMI
AF:
0.140
Gnomad AMR
AF:
0.291
Gnomad ASJ
AF:
0.472
Gnomad EAS
AF:
0.455
Gnomad SAS
AF:
0.306
Gnomad FIN
AF:
0.161
Gnomad MID
AF:
0.408
Gnomad NFE
AF:
0.164
Gnomad OTH
AF:
0.273
GnomAD2 exomes
AF:
0.243
AC:
60808
AN:
250266
AF XY:
0.244
show subpopulations
Gnomad AFR exome
AF:
0.205
Gnomad AMR exome
AF:
0.305
Gnomad ASJ exome
AF:
0.463
Gnomad EAS exome
AF:
0.461
Gnomad FIN exome
AF:
0.165
Gnomad NFE exome
AF:
0.171
Gnomad OTH exome
AF:
0.270
GnomAD4 exome
AF:
0.170
AC:
247737
AN:
1460236
Hom.:
28811
Cov.:
32
AF XY:
0.176
AC XY:
128026
AN XY:
726434
show subpopulations
African (AFR)
AF:
0.215
AC:
7190
AN:
33388
American (AMR)
AF:
0.303
AC:
13474
AN:
44536
Ashkenazi Jewish (ASJ)
AF:
0.459
AC:
11941
AN:
26032
East Asian (EAS)
AF:
0.468
AC:
18522
AN:
39546
South Asian (SAS)
AF:
0.300
AC:
25813
AN:
86028
European-Finnish (FIN)
AF:
0.167
AC:
8906
AN:
53350
Middle Eastern (MID)
AF:
0.379
AC:
2180
AN:
5754
European-Non Finnish (NFE)
AF:
0.132
AC:
146569
AN:
1111300
Other (OTH)
AF:
0.218
AC:
13142
AN:
60302
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.480
Heterozygous variant carriers
0
11767
23534
35301
47068
58835
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5142
10284
15426
20568
25710
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.211
AC:
32070
AN:
152150
Hom.:
3955
Cov.:
32
AF XY:
0.217
AC XY:
16110
AN XY:
74382
show subpopulations
African (AFR)
AF:
0.203
AC:
8443
AN:
41526
American (AMR)
AF:
0.291
AC:
4445
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.472
AC:
1638
AN:
3470
East Asian (EAS)
AF:
0.456
AC:
2353
AN:
5162
South Asian (SAS)
AF:
0.307
AC:
1478
AN:
4818
European-Finnish (FIN)
AF:
0.161
AC:
1703
AN:
10594
Middle Eastern (MID)
AF:
0.415
AC:
122
AN:
294
European-Non Finnish (NFE)
AF:
0.164
AC:
11173
AN:
67990
Other (OTH)
AF:
0.279
AC:
588
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1237
2474
3711
4948
6185
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
338
676
1014
1352
1690
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.201
Hom.:
14653
Bravo
AF:
0.220
TwinsUK
AF:
0.125
AC:
465
ALSPAC
AF:
0.121
AC:
466
ESP6500AA
AF:
0.199
AC:
877
ESP6500EA
AF:
0.175
AC:
1508
ExAC
AF:
0.240
AC:
29102
Asia WGS
AF:
0.375
AC:
1301
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
23
DANN
Benign
0.91
DEOGEN2
Benign
0.0074
.;T;.;.;.
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
.;D;D;D;D
MetaRNN
Benign
0.0027
T;T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.69
.;N;.;.;N
PhyloP100
7.0
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.57
N;N;N;.;N
REVEL
Benign
0.11
Sift
Benign
0.33
T;T;T;.;T
Sift4G
Benign
0.37
T;T;T;T;T
Polyphen
0.93
.;P;.;.;.
Vest4
0.13
MPC
0.25
ClinPred
0.047
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.22
Mutation Taster
=64/36
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00093
dbscSNV1_RF
Benign
0.0040
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

Other links and lift over

dbSNP: rs961360; hg19: chr2-136393658; COSMIC: COSV51520564; COSMIC: COSV51520564; API