X-155614626-A-T

Position:

• chrX-155614626-A-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+1979A>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 0.66 (17697 hom., 21440 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: SPRY3 NM_001304990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.691

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRY3	NM_001304990.2	c.-282+1979A>T		intron_variant		ENST00000695325.1	NP_001291919.1
SPRY3	NM_001394353.1	c.-441+1979A>T		intron_variant			NP_001381282.1
SPRY3	NM_001394354.1	c.-350+1979A>T		intron_variant			NP_001381283.1
SPRY3	NM_001394355.1	c.-719+1979A>T		intron_variant			NP_001381284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRY3	ENST00000695325.1	c.-282+1979A>T		intron_variant			NM_001304990.2	ENSP00000511806	P1
SPRY3	ENST00000675360.1	c.-441+1979A>T		intron_variant				ENSP00000502489	P1
TMLHE	ENST00000675642.1	c.32+55132T>A		intron_variant				ENSP00000502604
SPRY3	ENST00000676089.1	n.76+1979A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.661 AC: 72713 AN: 110017 Hom.: 17695 Cov.: 22 AF XY: 0.662 AC XY: 21392 AN XY: 32293

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.671

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: 0.661 AC: 72752 AN: 110071 Hom.: 17697 Cov.: 22 AF XY: 0.663 AC XY: 21440 AN XY: 32357

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.663

Alfa AF: 0.693 Hom.: 5540

Bravo AF: 0.646

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs479901; hg19: chrX-154844287;