X-155670185-A-G

Position:

• chrX-155670185-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001304990.2(SPRY3):​c.-282+57538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 110,429 control chromosomes in the GnomAD database, including 14,230 homozygotes. There are 18,124 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 0.55 (14230 hom., 18124 hem., cov: 22)
• Consequence: SPRY3 NM_001304990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRY3	NM_001304990.2	c.-282+57538A>G		intron_variant		ENST00000695325.1	NP_001291919.1
SPRY3	NM_001394353.1	c.-282+13160A>G		intron_variant			NP_001381282.1
SPRY3	NM_001394354.1	c.-350+57538A>G		intron_variant			NP_001381283.1
SPRY3	NM_001394355.1	c.-719+57538A>G		intron_variant			NP_001381284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRY3	ENST00000695325.1	c.-282+57538A>G		intron_variant			NM_001304990.2	ENSP00000511806	P1
SPRY3	ENST00000675360.1	c.-282+13160A>G		intron_variant				ENSP00000502489	P1
TMLHE	ENST00000675642.1	c.-152-244T>C		intron_variant				ENSP00000502604
SPRY3	ENST00000676089.1	n.76+57538A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.547 AC: 60405 AN: 110377 Hom.: 14234 Cov.: 22 AF XY: 0.552 AC XY: 18110 AN XY: 32781

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.547 AC: 60399 AN: 110429 Hom.: 14230 Cov.: 22 AF XY: 0.552 AC XY: 18124 AN XY: 32843

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.571

Alfa AF: 0.677 Hom.: 19235

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs473491; hg19: chrX-154899846;