rs12494774

Positions:

• chr3-129890314-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001017395.5(TMCC1):​c.-435+3180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 152,246 control chromosomes in the GnomAD database, including 676 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 0.082 (676 hom., cov: 33)
• Consequence: TMCC1 NM_001017395.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCC1	NM_001017395.5	c.-435+3180C>T		intron_variant		ENST00000393238.8	NP_001017395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCC1	ENST00000393238.8	c.-435+3180C>T		intron_variant		1	NM_001017395.5	ENSP00000376930	P3

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 12408 AN: 152128 Hom.: 674 Cov.: 33

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0804

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

GnomAD4 genome AF: 0.0815 AC: 12412 AN: 152246 Hom.: 676 Cov.: 33 AF XY: 0.0839 AC XY: 6244 AN XY: 74438

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0666

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0835 Hom.: 348

Bravo AF: 0.0842

Asia WGS AF: 0.136 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12494774; hg19: chr3-129609157;