rs886045701

Variant names:

• chr1-18871646-T-C
• NM_003748.4:c.*1199A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-18871646-T-C
• chr1-18871646-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003748.4(ALDH4A1):​c.*1199A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ALDH4A1 NM_003748.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

Genes affected

ALDH4A1 (HGNC:406): (aldehyde dehydrogenase 4 family member A1) This protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH4A1	NM_003748.4	c.*1199A>G		3_prime_UTR_variant	Exon 15 of 15	ENST00000375341.8	NP_003739.2
ALDH4A1	NM_170726.3	c.*186A>G		3_prime_UTR_variant	Exon 16 of 16		NP_733844.1
ALDH4A1	NM_001319218.2	c.*1199A>G		3_prime_UTR_variant	Exon 14 of 14		NP_001306147.1
ALDH4A1	NM_001161504.2	c.*1199A>G		3_prime_UTR_variant	Exon 15 of 15		NP_001154976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH4A1	ENST00000375341	c.*1199A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_003748.4	ENSP00000364490.3
ALDH4A1	ENST00000290597	c.*186A>G		3_prime_UTR_variant	Exon 16 of 16	1		ENSP00000290597.5
ALDH4A1	ENST00000538839	c.*1199A>G		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000446071.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-19198140;