rs574386

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

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

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRY3	ENST00000695325.1	c.-282+5181C>G		intron_variant			NM_001304990.2	ENSP00000511806	P1
SPRY3	ENST00000675360.1	c.-441+5181C>G		intron_variant				ENSP00000502489	P1
TMLHE	ENST00000675642.1	c.32+51930G>C		intron_variant				ENSP00000502604
SPRY3	ENST00000676089.1	n.76+5181C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000190 AC: 21 AN: 110253 Hom.: 0 Cov.: 22 AF XY: 0.000154 AC XY: 5 AN XY: 32529

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

Gnomad4 AFR AF: 0.0000330

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000380

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000577 Hom.: 4309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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;