rs672932

Variant names:

• chrX-155686314-G-A
• rs672932
• NM_001304990.2:c.-282+73667G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304990.2(SPRY3):​c.-282+73667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 110,201 control chromosomes in the GnomAD database, including 5,745 homozygotes. There are 10,745 hemizygotes in GnomAD. 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 0.34 (5745 hom., 10745 hem., cov: 22)
• Consequence: SPRY3 NM_001304990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 0 publications found

Genes affected

SPRY3 (HGNC:11271): (sprouty RTK signaling antagonist 3) Involved in negative regulation of MAPK cascade. Predicted to be located in membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TMLHE (HGNC:18308): (trimethyllysine hydroxylase, epsilon) This gene encodes the protein trimethyllysine dioxygenase which is the first enzyme in the carnitine biosynthesis pathway. Carnitine play an essential role in the transport of activated fatty acids across the inner mitochondrial membrane. The encoded protein converts trimethyllysine into hydroxytrimethyllysine. A pseudogene of this gene is found on chromosome X. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

TMLHE Gene-Disease associations (from GenCC):

• epsilon-trimethyllysine hydroxylase deficiency

  Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• autism spectrum disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304990.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRY3	NM_001304990.2	MANE Select	c.-282+73667G>A		intron	N/A	NP_001291919.1	O43610
	SPRY3	NM_001394353.1		c.-282+29289G>A		intron	N/A	NP_001381282.1	O43610
	SPRY3	NM_001394354.1		c.-349-50594G>A		intron	N/A	NP_001381283.1	O43610

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRY3	ENST00000695325.1	MANE Select	c.-282+73667G>A		intron	N/A	ENSP00000511806.1	O43610
	TMLHE	ENST00000675642.1		c.-152-16373C>T		intron	N/A	ENSP00000502604.1	Q9NVH6-8
	TMLHE	ENST00000902548.1		c.-2+32713C>T		intron	N/A	ENSP00000572607.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 37846 AN: 110151 Hom.: 5737 Cov.: 22

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.344 AC: 37872 AN: 110201 Hom.: 5745 Cov.: 22 AF XY: 0.330 AC XY: 10745 AN XY: 32529

African (AFR) AF: 0.583 AC: 17610 AN: 30226

American (AMR) AF: 0.332 AC: 3429 AN: 10338

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 616 AN: 2628

East Asian (EAS) AF: 0.273 AC: 956 AN: 3502

South Asian (SAS) AF: 0.256 AC: 669 AN: 2617

European-Finnish (FIN) AF: 0.221 AC: 1278 AN: 5789

Middle Eastern (MID) AF: 0.190 AC: 40 AN: 211

European-Non Finnish (NFE) AF: 0.238 AC: 12562 AN: 52708

Other (OTH) AF: 0.334 AC: 504 AN: 1507

Alfa AF: 0.303 Hom.: 2156

Bravo AF: 0.364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.41
PhyloP100		0.056

Splicing

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

Other links and lift over

dbSNP: rs672932; hg19: chrX-154915975;