2-96254918-G-T

Variant names:

• chr2-96254918-G-T
• rs148381232
• NM_017849.4:c.324C>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017849.4(TMEM127):​c.324C>A​(p.Leu108Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TMEM127 NM_017849.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=0.541 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM127	NM_017849.4	c.324C>A	p.Leu108Leu	synonymous_variant	Exon 3 of 4	ENST00000258439.8	NP_060319.1
TMEM127	NM_001193304.3	c.324C>A	p.Leu108Leu	synonymous_variant	Exon 3 of 4		NP_001180233.1
TMEM127	NM_001407282.1	c.72C>A	p.Leu24Leu	synonymous_variant	Exon 2 of 3		NP_001394211.1
TMEM127	NM_001407283.1	c.72C>A	p.Leu24Leu	synonymous_variant	Exon 2 of 3		NP_001394212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM127	ENST00000258439.8	c.324C>A	p.Leu108Leu	synonymous_variant	Exon 3 of 4	1	NM_017849.4	ENSP00000258439.3
TMEM127	ENST00000432959.1	c.324C>A	p.Leu108Leu	synonymous_variant	Exon 3 of 4	1		ENSP00000416660.1
TMEM127	ENST00000435268.1	c.72C>A	p.Leu24Leu	synonymous_variant	Exon 2 of 3	3		ENSP00000411810.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.1
DANN	Benign	0.86

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: rs148381232; hg19: chr2-96920656;