19-18612515-T-C

Position:

• chr19-18612515-T-C

Variant summary

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

The ENST00000600490.5(TMEM59L):​c.-108-336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,860 control chromosomes in the GnomAD database, including 34,707 homozygotes. 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 (34707 hom., cov: 30)
• Consequence: TMEM59L ENST00000600490.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

Genes affected

TMEM59L (HGNC:13237): (transmembrane protein 59 like) This gene encodes a predicted type-I membrane glycoprotein. The encoded protein may play a role in functioning of the central nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM59L	ENST00000600490.5	c.-108-336T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100641 AN: 151744 Hom.: 34656 Cov.: 30

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.663 AC: 100750 AN: 151860 Hom.: 34707 Cov.: 30 AF XY: 0.661 AC XY: 49034 AN XY: 74218

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.618

Alfa AF: 0.618 Hom.: 9174

Bravo AF: 0.669

Asia WGS AF: 0.600 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7250192; hg19: chr19-18723325;