chr17-3489774-T-C

Position:

• chr17-3489774-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000049.4(ASPA):​c.634+432T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,964 control chromosomes in the GnomAD database, including 5,101 homozygotes. 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 0.23 (5101 hom., cov: 33)
• Consequence: ASPA NM_000049.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

Genes affected

ASPA (HGNC:756): (aspartoacylase) This gene encodes an enzyme that catalyzes the conversion of N-acetyl_L-aspartic acid (NAA) to aspartate and acetate. NAA is abundant in the brain where hydrolysis by aspartoacylase is thought to help maintain white matter. This protein is an NAA scavenger in other tissues. Mutations in this gene cause Canavan disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

SPATA22 (HGNC:30705): (spermatogenesis associated 22) Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASPA	NM_000049.4	c.634+432T>C		intron_variant		ENST00000263080.3	NP_000040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASPA	ENST00000263080.3	c.634+432T>C		intron_variant		1	NM_000049.4	ENSP00000263080.2
ASPA	ENST00000456349.6	c.634+432T>C		intron_variant		1		ENSP00000409976.2
SPATA22	ENST00000541913.5	c.-73-20376A>G		intron_variant		2		ENSP00000441920.1
SPATA22	ENST00000570318.1	c.-73-20376A>G		intron_variant		2		ENSP00000459147.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35492 AN: 151844 Hom.: 5084 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.234 AC: 35556 AN: 151964 Hom.: 5101 Cov.: 33 AF XY: 0.229 AC XY: 17022 AN XY: 74310

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.229

Alfa AF: 0.170 Hom.: 1988

Bravo AF: 0.246

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs923375; hg19: chr17-3393068;