X-155614626-A-T

Variant names:

• chrX-155614626-A-T
• rs479901
• NM_001304990.2:c.-282+1979A>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+1979A>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 0.66 (17697 hom., 21440 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: SPRY3 NM_001304990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.691
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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+1979A>T		intron	N/A	NP_001291919.1	O43610
	SPRY3	NM_001394353.1		c.-441+1979A>T		intron	N/A	NP_001381282.1	O43610
	SPRY3	NM_001394354.1		c.-350+1979A>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+1979A>T		intron	N/A	ENSP00000511806.1	O43610
	TMLHE	ENST00000675642.1		c.32+55132T>A		intron	N/A	ENSP00000502604.1	Q9NVH6-8
	TMLHE	ENST00000902548.1		c.-1-69349T>A		intron	N/A	ENSP00000572607.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 72713 AN: 110017 Hom.: 17695 Cov.: 22

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.671

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: 0.661 AC: 72752 AN: 110071 Hom.: 17697 Cov.: 22 AF XY: 0.663 AC XY: 21440 AN XY: 32357

African (AFR) AF: 0.452 AC: 13722 AN: 30358

American (AMR) AF: 0.663 AC: 6905 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 1994 AN: 2615

East Asian (EAS) AF: 0.721 AC: 2495 AN: 3461

South Asian (SAS) AF: 0.723 AC: 1855 AN: 2564

European-Finnish (FIN) AF: 0.761 AC: 4345 AN: 5713

Middle Eastern (MID) AF: 0.796 AC: 168 AN: 211

European-Non Finnish (NFE) AF: 0.757 AC: 39815 AN: 52571

Other (OTH) AF: 0.663 AC: 991 AN: 1495

Alfa AF: 0.693 Hom.: 5540

Bravo AF: 0.646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.36
PhyloP100		0.69

Splicing

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

Other links and lift over

dbSNP: rs479901; hg19: chrX-154844287;