rs72624961

Variant names:

• chr7-128396989-C-G
• rs72624961
• NM_000883.4:c.1108G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-128396989-C-G
• chr7-128396989-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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: 𝑓 0.000020 (0 hom., cov: 33)
• Consequence: IMPDH1 NM_000883.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• Publications: 8 publications found

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]

IMPDH1 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Leber congenital amaurosis 11

  Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa 10

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000883.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	NM_000883.4	MANE Select	c.1108G>C	p.Ala370Pro	missense	Exon 11 of 17	NP_000874.2
	IMPDH1	NM_001102605.2		c.1078G>C	p.Ala360Pro	missense	Exon 10 of 16	NP_001096075.1
	IMPDH1	NM_001142576.2		c.1009G>C	p.Ala337Pro	missense	Exon 10 of 16	NP_001136048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPDH1	ENST00000338791.11	TSL:2 MANE Select	c.1108G>C	p.Ala370Pro	missense	Exon 11 of 17	ENSP00000345096.6
	IMPDH1	ENST00000348127.11	TSL:1	c.1000G>C	p.Ala334Pro	missense	Exon 9 of 15	ENSP00000265385.8
	IMPDH1	ENST00000354269.9	TSL:2	c.1078G>C	p.Ala360Pro	missense	Exon 10 of 16	ENSP00000346219.5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152114 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251448 AF XY: 0.00000736

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 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

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.035
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.55	T
PhyloP100		2.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.34	N
REVEL	Uncertain	0.31
Sift	Benign	0.098	T
Sift4G	Uncertain	0.026	D
Polyphen		0.0010	B
Vest4		0.68
MVP		0.65
MPC		0.71
ClinPred		0.48	T
GERP RS		5.2
gMVP		0.92
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs72624961; hg19: chr7-128037043;