3-129864041-C-G

Position:

• chr3-129864041-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017395.5(TMCC1):​c.-184+16268G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,066 control chromosomes in the GnomAD database, including 35,167 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 0.63 (35167 hom., cov: 32)
• Consequence: TMCC1 NM_001017395.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

Genes affected

TMCC1 (HGNC:29116): (transmembrane and coiled-coil domain family 1) Enables identical protein binding activity. Involved in several processes, including endosome fission; endosome membrane tubulation; and membrane fission. Located in cytosol; endoplasmic reticulum-endosome membrane contact site; and rough endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMCC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCC1	NM_001017395.5	c.-184+16268G>C		intron_variant		ENST00000393238.8	NP_001017395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCC1	ENST00000393238.8	c.-184+16268G>C		intron_variant		1	NM_001017395.5	ENSP00000376930.3

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95086 AN: 151946 Hom.: 35158 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.625 AC: 95104 AN: 152066 Hom.: 35167 Cov.: 32 AF XY: 0.625 AC XY: 46497 AN XY: 74340

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.667

Alfa AF: 0.637 Hom.: 2482

Bravo AF: 0.596

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.72

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: rs2811337; hg19: chr3-129582884;