rs12494774

Variant names:

• chr3-129890314-G-A
• rs12494774
• NM_001017395.5:c.-435+3180C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017395.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC1	NM_001017395.5	MANE Select	c.-435+3180C>T		intron	N/A	NP_001017395.2
	TMCC1	NM_001349263.2		c.-598+3180C>T		intron	N/A	NP_001336192.1
	TMCC1	NM_001349264.2		c.-438+3180C>T		intron	N/A	NP_001336193.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC1	ENST00000393238.8	TSL:1 MANE Select	c.-435+3180C>T		intron	N/A	ENSP00000376930.3
	TMCC1	ENST00000426664.6	TSL:5	c.-95+3180C>T		intron	N/A	ENSP00000389892.2
	TMCC1	ENST00000648771.1		c.-863-1210C>T		intron	N/A	ENSP00000497993.1

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

African (AFR) AF: 0.0401 AC: 1666 AN: 41556

American (AMR) AF: 0.144 AC: 2209 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.173 AC: 894 AN: 5170

South Asian (SAS) AF: 0.116 AC: 559 AN: 4816

European-Finnish (FIN) AF: 0.0666 AC: 706 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5691 AN: 68026

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0801 Hom.: 506

Bravo AF: 0.0842

Asia WGS AF: 0.136 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.69
PhyloP100		2.2
Mutation Taster		=91/9	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12494774; hg19: chr3-129609157;