chr17-3489774-T-C

Variant names:

• chr17-3489774-T-C
• rs923375
• NM_000049.4:c.634+432T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

SPATA22 Gene-Disease associations (from GenCC):

• infertility disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ASPA	NM_000049.4	c.634+432T>C		intron_variant	Intron 4 of 5	ENST00000263080.3	NP_000040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASPA	ENST00000263080.3	c.634+432T>C		intron_variant	Intron 4 of 5	1	NM_000049.4	ENSP00000263080.2
ASPA	ENST00000456349.6	c.634+432T>C		intron_variant	Intron 5 of 6	1		ENSP00000409976.2
SPATA22	ENST00000541913.5	c.-73-20376A>G		intron_variant	Intron 1 of 8	2		ENSP00000441920.1
SPATA22	ENST00000570318.1	c.-73-20376A>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.414 AC: 17138 AN: 41352

American (AMR) AF: 0.174 AC: 2661 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1200 AN: 5174

South Asian (SAS) AF: 0.263 AC: 1266 AN: 4818

European-Finnish (FIN) AF: 0.0991 AC: 1050 AN: 10592

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10941 AN: 67960

Other (OTH) AF: 0.229 AC: 484 AN: 2110

Alfa AF: 0.192 Hom.: 8746

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
PhyloP100		-0.043
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: rs923375; hg19: chr17-3393068;