Menu
GeneBe

6-49607187-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP7BS1_Supporting

The NM_000324.3(RHAG):c.1101C>T(p.Ser367=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

RHAG
NM_000324.3 synonymous

Scores

10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.714
Variant links:
Genes affected
RHAG (HGNC:10006): (Rh associated glycoprotein) The protein encoded by this gene is erythrocyte-specific and is thought to be part of a membrane channel that transports ammonium and carbon dioxide across the blood cell membrane. The encoded protein appears to interact with Rh blood group antigens and Rh30 polypeptides. Defects in this gene are a cause of regulator type Rh-null hemolytic anemia (RHN), or Rh-deficiency syndrome.[provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.017772853).
BP7
Synonymous conserved (PhyloP=-0.714 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000267 (39/1461544) while in subpopulation AFR AF= 0.00105 (35/33468). AF 95% confidence interval is 0.000772. There are 0 homozygotes in gnomad4_exome. There are 11 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RHAGNM_000324.3 linkuse as main transcriptc.1101C>T p.Ser367= synonymous_variant 8/10 ENST00000371175.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHAGENST00000371175.10 linkuse as main transcriptc.1101C>T p.Ser367= synonymous_variant 8/101 NM_000324.3 P2Q02094-1
RHAGENST00000646939.1 linkuse as main transcriptc.979C>T p.Leu327Phe missense_variant 7/9 Q02094-2
RHAGENST00000646272.1 linkuse as main transcriptc.1101C>T p.Ser367= synonymous_variant 8/10 A2
RHAGENST00000646963.1 linkuse as main transcriptc.1101C>T p.Ser367= synonymous_variant 8/9

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000603
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000958
AC:
24
AN:
250446
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135312
show subpopulations
Gnomad AFR exome
AF:
0.00142
Gnomad AMR exome
AF:
0.0000290
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461544
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
727062
show subpopulations
Gnomad4 AFR exome
AF:
0.00105
Gnomad4 AMR exome
AF:
0.0000672
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.000135
AC XY:
10
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.000603
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000155
Hom.:
0
Bravo
AF:
0.000283
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000989
AC:
12

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityNov 14, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
3.1
Dann
Benign
0.91
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.20
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
D;N
GERP RS
-8.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs139371066; hg19: chr6-49574900; API