chr12-94608764-C-A

Variant names:

• chr12-94608764-C-A
• rs12426730
• NM_020698.4:c.79-26226G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMCC3	NM_020698.4	c.79-26226G>T		intron_variant	Intron 1 of 3	ENST00000261226.9	NP_065749.3
TMCC3	NM_001301036.2	c.-16+7159G>T		intron_variant	Intron 1 of 3		NP_001287965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCC3	ENST00000261226.9	c.79-26226G>T		intron_variant	Intron 1 of 3	1	NM_020698.4	ENSP00000261226.4
TMCC3	ENST00000551457.1	c.-16+7159G>T		intron_variant	Intron 1 of 3	1		ENSP00000449888.1
TMCC3	ENST00000548918.1	c.-16+7586G>T		intron_variant	Intron 1 of 1	2		ENSP00000450078.1

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

African (AFR) AF: 0.0558 AC: 2318 AN: 41522

American (AMR) AF: 0.0625 AC: 956 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 293 AN: 3466

East Asian (EAS) AF: 0.0992 AC: 514 AN: 5182

South Asian (SAS) AF: 0.139 AC: 671 AN: 4824

European-Finnish (FIN) AF: 0.0518 AC: 549 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5118 AN: 68012

Other (OTH) AF: 0.0687 AC: 145 AN: 2112

Alfa AF: 0.0743 Hom.: 727

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
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12426730; hg19: chr12-95002540;