chr19-18612515-T-C

Variant names:

• chr19-18612515-T-C
• rs7250192
• ENST00000600490.5:c.-108-336T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000300180 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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
ENSG00000300180	ENST00000769788.1	n.-1A>G		upstream_gene_variant

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

African (AFR) AF: 0.863 AC: 35748 AN: 41440

American (AMR) AF: 0.593 AC: 9053 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1719 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3228 AN: 5132

South Asian (SAS) AF: 0.466 AC: 2234 AN: 4796

European-Finnish (FIN) AF: 0.665 AC: 7029 AN: 10562

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39778 AN: 67880

Other (OTH) AF: 0.618 AC: 1303 AN: 2110

Alfa AF: 0.623 Hom.: 11704

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
PhyloP100		-0.023
PromoterAI		0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7250192; hg19: chr19-18723325;