ENST00000807688.1:n.292-14864C>T

Variant names:

• chr2-62486398-C-T
• rs6545946
• ENST00000807688.1:n.292-14864C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000807688.1(ENSG00000228541):​n.292-14864C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,090 control chromosomes in the GnomAD database, including 4,922 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 0.25 (4922 hom., cov: 32)
• Consequence: ENSG00000228541 ENST00000807688.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 25 publications found

Genes affected

ENSG00000228541 (HGNC:):

TMEM17 (HGNC:26623): (transmembrane protein 17) Involved in non-motile cilium assembly. Predicted to be located in ciliary membrane. Predicted to be part of MKS complex. Predicted to be active in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM17	XM_024452749.2	c.318+16039G>A		intron_variant	Intron 3 of 5		XP_024308517.1
TMEM17	XM_011532693.3	c.319-3650G>A		intron_variant	Intron 3 of 3		XP_011530995.1
TMEM17	XM_011532694.3	c.318+16039G>A		intron_variant	Intron 3 of 4		XP_011530996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228541	ENST00000807688.1	n.292-14864C>T		intron_variant	Intron 1 of 1
ENSG00000228541	ENST00000807713.1	n.270+7762C>T		intron_variant	Intron 1 of 4
ENSG00000228541	ENST00000807714.1	n.167-14864C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37897 AN: 151972 Hom.: 4919 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.249 AC: 37941 AN: 152090 Hom.: 4922 Cov.: 32 AF XY: 0.249 AC XY: 18499 AN XY: 74332

African (AFR) AF: 0.319 AC: 13212 AN: 41470

American (AMR) AF: 0.213 AC: 3251 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3472

East Asian (EAS) AF: 0.157 AC: 812 AN: 5182

South Asian (SAS) AF: 0.229 AC: 1101 AN: 4818

European-Finnish (FIN) AF: 0.278 AC: 2936 AN: 10570

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15188 AN: 67982

Other (OTH) AF: 0.220 AC: 464 AN: 2110

Alfa AF: 0.229 Hom.: 17418

Bravo AF: 0.248

Asia WGS AF: 0.198 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.52
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs6545946; hg19: chr2-62713533;