rs574386

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-155617828-C-G
• chrX-155617828-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001304990.2(SPRY3):​c.-282+5181C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 110,253 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 0.00019 (0 hom., 5 hem., cov: 22)
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BS2: High Hemizygotes in GnomAd4 at 5 gene

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

Frequencies

GnomAD3 genomes AF: 0.000190 AC: 21 AN: 110253 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000380

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000190 AC: 21 AN: 110253 Hom.: 0 Cov.: 22 AF XY: 0.000154 AC XY: 5 AN XY: 32529

African (AFR) AF: 0.0000330 AC: 1 AN: 30333

American (AMR) AF: 0.00 AC: 0 AN: 10391

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2630

East Asian (EAS) AF: 0.00 AC: 0 AN: 3494

South Asian (SAS) AF: 0.00 AC: 0 AN: 2601

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.000380 AC: 20 AN: 52691

Other (OTH) AF: 0.00 AC: 0 AN: 1470

Alfa AF: 0.0000577 Hom.: 4309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.54
DANN	Benign	0.37
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;