12-94570381-T-C

Variant names:

• chr12-94570381-T-C
• rs1290005
• NM_020698.4:c.*1054A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020698.4(TMCC3):​c.*1054A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,150 control chromosomes in the GnomAD database, including 35,456 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 0.68 (35455 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: TMCC3 NM_020698.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317
• Publications: 7 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCC3	NM_020698.4	c.*1054A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000261226.9	NP_065749.3
TMCC3	NM_001301036.2	c.*1054A>G		3_prime_UTR_variant	Exon 4 of 4		NP_001287965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCC3	ENST00000261226.9	c.*1054A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_020698.4	ENSP00000261226.4
TMCC3	ENST00000551457.1	c.*1054A>G		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000449888.1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103547 AN: 152028 Hom.: 35427 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.672

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.681 AC: 103615 AN: 152146 Hom.: 35455 Cov.: 32 AF XY: 0.680 AC XY: 50539 AN XY: 74362

African (AFR) AF: 0.737 AC: 30596 AN: 41504

American (AMR) AF: 0.660 AC: 10084 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2409 AN: 3472

East Asian (EAS) AF: 0.493 AC: 2547 AN: 5170

South Asian (SAS) AF: 0.654 AC: 3162 AN: 4832

European-Finnish (FIN) AF: 0.683 AC: 7224 AN: 10584

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45334 AN: 67980

Other (OTH) AF: 0.675 AC: 1422 AN: 2108

Alfa AF: 0.668 Hom.: 103031

Bravo AF: 0.681

Asia WGS AF: 0.644 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1290005; hg19: chr12-94964157;