rs672932

chrX-155686314-G-A

Variant summary

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

The NM_001304990.2(SPRY3):c.-282+73667G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 110,201 control chromosomes in the GnomAD database, including 5,745 homozygotes. There are 10,745 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 0.34 (5745 hom., 10745 hem., cov: 22)
• Consequence: SPRY3 NM_001304990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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 (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRY3	NM_001304990.2	c.-282+73667G>A		intron_variant		ENST00000695325.1
SPRY3	NM_001394353.1	c.-282+29289G>A		intron_variant
SPRY3	NM_001394354.1	c.-349-50594G>A		intron_variant
SPRY3	NM_001394355.1	c.-719+73667G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRY3	ENST00000695325.1	c.-282+73667G>A		intron_variant			NM_001304990.2	P1
SPRY3	ENST00000675360.1	c.-282+29289G>A		intron_variant				P1
TMLHE	ENST00000675642.1	c.-152-16373C>T		intron_variant
SPRY3	ENST00000676089.1	n.77-50594G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.344 AC: 37846 AN: 110151 Hom.: 5737 Cov.: 22 AF XY: 0.330 AC XY: 10722 AN XY: 32469

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.344 AC: 37872 AN: 110201 Hom.: 5745 Cov.: 22 AF XY: 0.330 AC XY: 10745 AN XY: 32529

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.334

Alfa AF: 0.303 Hom.: 2156

Bravo AF: 0.364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.61
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: rs672932; hg19: chrX-154915975;