rs2016108

Variant names:

• chr22-18928450-G-A
• rs2016108
• NM_016335.6:c.482+2540C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-18928450-G-A
• chr22-18928450-G-C
• chr22-18928450-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016335.6(PRODH):​c.482+2540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (2144 hom., cov: 5)
  • Failed GnomAD Quality Control
• Consequence: PRODH NM_016335.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750
• Publications: 7 publications found

Genes affected

PRODH (HGNC:9453): (proline dehydrogenase 1) This gene encodes a mitochondrial protein that catalyzes the first step in proline degradation. Mutations in this gene are associated with hyperprolinemia type 1 and susceptibility to schizophrenia 4 (SCZD4). This gene is located on chromosome 22q11.21, a region which has also been associated with the contiguous gene deletion syndromes, DiGeorge and CATCH22. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

PRODH Gene-Disease associations (from GenCC):

• hyperprolinemia type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000283809 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRODH	NM_016335.6	c.482+2540C>T		intron_variant	Intron 2 of 13	ENST00000357068.11	NP_057419.5
PRODH	NM_001195226.2	c.158+2540C>T		intron_variant	Intron 2 of 13		NP_001182155.2
PRODH	NM_001368250.2	c.158+2540C>T		intron_variant	Intron 2 of 13		NP_001355179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRODH	ENST00000357068.11	c.482+2540C>T		intron_variant	Intron 2 of 13	1	NM_016335.6	ENSP00000349577.6
ENSG00000283809	ENST00000638240.1	c.514-11223G>A		intron_variant	Intron 4 of 5	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 8911 AN: 22824 Hom.: 2131 Cov.: 5

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.363

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.391 AC: 8947 AN: 22886 Hom.: 2144 Cov.: 5 AF XY: 0.386 AC XY: 4087 AN XY: 10596

African (AFR) AF: 0.521 AC: 3908 AN: 7502

American (AMR) AF: 0.439 AC: 935 AN: 2132

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 240 AN: 666

East Asian (EAS) AF: 0.714 AC: 720 AN: 1008

South Asian (SAS) AF: 0.278 AC: 113 AN: 406

European-Finnish (FIN) AF: 0.274 AC: 285 AN: 1042

Middle Eastern (MID) AF: 0.232 AC: 13 AN: 56

European-Non Finnish (NFE) AF: 0.269 AC: 2598 AN: 9660

Other (OTH) AF: 0.356 AC: 99 AN: 278

Alfa AF: 0.231 Hom.: 8568

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs2016108; hg19: chr22-18915963;