NM_001304990.2:c.-282+5181C>T

Variant names:

• chrX-155617828-C-T
• rs574386
• NM_001304990.2:c.-282+5181C>T

Variant summary

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

The NM_001304990.2(SPRY3):​c.-282+5181C>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 0.65 (17336 hom., 21489 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: SPRY3 NM_001304990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 5 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

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+5181C>T		intron	N/A	NP_001291919.1	O43610
	SPRY3	NM_001394353.1		c.-441+5181C>T		intron	N/A	NP_001381282.1	O43610
	SPRY3	NM_001394354.1		c.-350+5181C>T		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+5181C>T		intron	N/A	ENSP00000511806.1	O43610
	TMLHE	ENST00000675642.1		c.32+51930G>A		intron	N/A	ENSP00000502604.1	Q9NVH6-8
	TMLHE	ENST00000902548.1		c.-1-72551G>A		intron	N/A	ENSP00000572607.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 71909 AN: 110189 Hom.: 17336 Cov.: 22

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.669

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: InbreedingCoeff AF: 0.653 AC: 71936 AN: 110245 Hom.: 17336 Cov.: 22 AF XY: 0.660 AC XY: 21489 AN XY: 32569

African (AFR) AF: 0.416 AC: 12635 AN: 30378

American (AMR) AF: 0.662 AC: 6884 AN: 10399

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2006 AN: 2629

East Asian (EAS) AF: 0.724 AC: 2517 AN: 3477

South Asian (SAS) AF: 0.723 AC: 1878 AN: 2596

European-Finnish (FIN) AF: 0.775 AC: 4442 AN: 5735

Middle Eastern (MID) AF: 0.796 AC: 172 AN: 216

European-Non Finnish (NFE) AF: 0.759 AC: 39956 AN: 52661

Other (OTH) AF: 0.661 AC: 984 AN: 1488

Alfa AF: 0.588 Hom.: 4309

Bravo AF: 0.635

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.63
DANN	Benign	0.41
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs574386; hg19: chrX-154847489; COSMIC: COSV57687847;