rs479901

Variant names:

• chrX-155614626-A-C
• rs479901
• NM_001304990.2:c.-282+1979A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-155614626-A-C
• chrX-155614626-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001304990.2(SPRY3):​c.-282+1979A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 22)
• 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 Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• autism spectrum disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRY3	NM_001304990.2	c.-282+1979A>C		intron_variant	Intron 1 of 2	ENST00000695325.1	NP_001291919.1
SPRY3	NM_001394353.1	c.-441+1979A>C		intron_variant	Intron 1 of 3		NP_001381282.1
SPRY3	NM_001394354.1	c.-350+1979A>C		intron_variant	Intron 1 of 3		NP_001381283.1
SPRY3	NM_001394355.1	c.-719+1979A>C		intron_variant	Intron 1 of 3		NP_001381284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRY3	ENST00000695325.1	c.-282+1979A>C		intron_variant	Intron 1 of 2		NM_001304990.2	ENSP00000511806.1
TMLHE	ENST00000675642.1	c.32+55132T>G		intron_variant	Intron 2 of 8			ENSP00000502604.1
SPRY3	ENST00000675360.1	c.-441+1979A>C		intron_variant	Intron 1 of 3			ENSP00000502489.1
SPRY3	ENST00000676089.1	n.76+1979A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 22

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

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.16
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;