19-18612515-T-C

Variant names:

• chr19-18612515-T-C
• rs7250192
• ENST00000600490.5:c.-108-336T>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM59L	ENST00000600490.5	c.-108-336T>C		intron_variant	Intron 1 of 8	5		ENSP00000470879.1

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;