rs72624961

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000883.4(IMPDH1):​c.1108G>C​(p.Ala370Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A370T) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)

Consequence

IMPDH1
NM_000883.4 missense

Scores

7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.53
Variant links:
Genes affected
IMPDH1 (HGNC:6052): (inosine monophosphate dehydrogenase 1) The protein encoded by this gene acts as a homotetramer to regulate cell growth. The encoded protein is an enzyme that catalyzes the synthesis of xanthine monophosphate (XMP) from inosine-5'-monophosphate (IMP). This is the rate-limiting step in the de novo synthesis of guanine nucleotides. Defects in this gene are a cause of retinitis pigmentosa type 10 (RP10). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35419285).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IMPDH1NM_000883.4 linkc.1108G>C p.Ala370Pro missense_variant Exon 11 of 17 ENST00000338791.11 NP_000874.2 P20839-6B3KRZ3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IMPDH1ENST00000338791.11 linkc.1108G>C p.Ala370Pro missense_variant Exon 11 of 17 2 NM_000883.4 ENSP00000345096.6 P20839-6

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152114
Hom.:
0
Cov.:
33
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251448
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135914
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152114
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;.;.;.;T;.;T;.
Eigen
Benign
-0.035
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.75
T;T;T;T;T;T;.;T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.35
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.55
T
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.34
N;N;N;N;.;N;N;N
REVEL
Uncertain
0.31
Sift
Benign
0.098
T;T;T;T;.;T;T;T
Sift4G
Uncertain
0.026
D;D;D;D;D;D;D;D
Polyphen
0.0010, 0.020
.;.;B;.;.;B;.;.
Vest4
0.68
MVP
0.65
MPC
0.71
ClinPred
0.48
T
GERP RS
5.2
gMVP
0.92

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: rs72624961; hg19: chr7-128037043; API