2-96250919-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017849.4(TMEM127):c.*2888del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 229,012 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (0 hom.)
• Consequence: TMEM127 NM_017849.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

Genes affected

TMEM127 (HGNC:26038): (transmembrane protein 127) This gene encodes a transmembrane protein with four predicted transmembrane domains. The protein is associated with a subpopulation of vesicular organelles corresponding to early endosomal structures, with the Golgi, and with lysosomes, and may participate in protein trafficking between these structures. Mutations in this gene and several other genes cause pheochromocytomas. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-96250919-TA-T is Benign according to our data. Variant chr2-96250919-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 337453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00271 (413/152208) while in subpopulation NFE AF= 0.00506 (344/67986). AF 95% confidence interval is 0.00462. There are 2 homozygotes in gnomad4. There are 175 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 413 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM127	NM_017849.4	c.*2888del		3_prime_UTR_variant	4/4	ENST00000258439.8
TMEM127	NM_001193304.3	c.*2888del		3_prime_UTR_variant	4/4
TMEM127	NM_001407282.1	c.*2888del		3_prime_UTR_variant	3/3
TMEM127	NM_001407283.1	c.*2888del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM127	ENST00000258439.8	c.*2888del		3_prime_UTR_variant	4/4	1	NM_017849.4	P1

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 413 AN: 152090 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000850

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00506

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.00322 AC: 247 AN: 76804 Hom.: 0 Cov.: 0 AF XY: 0.00316 AC XY: 112 AN XY: 35404

Gnomad4 AFR exome AF: 0.00110

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00472

Gnomad4 OTH exome AF: 0.00233

GnomAD4 genome AF: 0.00271 AC: 413 AN: 152208 Hom.: 2 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74406

Gnomad4 AFR AF: 0.000939

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000850

Gnomad4 NFE AF: 0.00506

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00286 Hom.: 0

Bravo AF: 0.00255

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Pheochromocytoma Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs139762991; hg19: chr2-96916657;