rs12426730

chr12-94608764-C-A

Variant summary

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

The NM_020698.4(TMCC3):c.79-26226G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,218 control chromosomes in the GnomAD database, including 395 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 0.070 (395 hom., cov: 32)
• Consequence: TMCC3 NM_020698.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

Genes affected

TMCC3 (HGNC:29199): (transmembrane and coiled-coil domain family 3) Enables 14-3-3 protein binding activity and identical protein binding activity. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCC3	NM_020698.4	c.79-26226G>T		intron_variant		ENST00000261226.9
TMCC3	NM_001301036.2	c.-16+7159G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCC3	ENST00000261226.9	c.79-26226G>T		intron_variant		1	NM_020698.4	P1
TMCC3	ENST00000551457.1	c.-16+7159G>T		intron_variant		1
TMCC3	ENST00000548918.1	c.-16+7586G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10709 AN: 152100 Hom.: 394 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0699

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

GnomAD4 genome AF: 0.0703 AC: 10706 AN: 152218 Hom.: 395 Cov.: 32 AF XY: 0.0702 AC XY: 5228 AN XY: 74448

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.0845

Gnomad4 EAS AF: 0.0992

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.0687

Alfa AF: 0.0751 Hom.: 577

Bravo AF: 0.0696

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.28
Dann	Benign	0.41

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: rs12426730; hg19: chr12-95002540;