X-155617828-C-T

Position:

• chrX-155617828-C-T

Variant summary

Our verdict is Likely benign. Variant got -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

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]

SPRY3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRY3	NM_001304990.2	c.-282+5181C>T		intron_variant		ENST00000695325.1	NP_001291919.1
SPRY3	NM_001394353.1	c.-441+5181C>T		intron_variant			NP_001381282.1
SPRY3	NM_001394354.1	c.-350+5181C>T		intron_variant			NP_001381283.1
SPRY3	NM_001394355.1	c.-719+5181C>T		intron_variant			NP_001381284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRY3	ENST00000695325.1	c.-282+5181C>T		intron_variant			NM_001304990.2	ENSP00000511806.1
TMLHE	ENST00000675642.1	c.32+51930G>A		intron_variant				ENSP00000502604.1
SPRY3	ENST00000675360.1	c.-441+5181C>T		intron_variant				ENSP00000502489.1
SPRY3	ENST00000676089.1	n.76+5181C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.653 AC: 71909 AN: 110189 Hom.: 17336 Cov.: 22 AF XY: 0.660 AC XY: 21447 AN XY: 32503

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

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.661

Alfa AF: 0.588 Hom.: 4309

Bravo AF: 0.635

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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