rs1172113

Positions:

• chr1-205257160-T-C

Variant summary

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

The NM_014858.4(TMCC2):​c.748-11790T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,232,424 control chromosomes in the GnomAD database, including 93,492 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 0.32 (8605 hom., cov: 32)
  • Exomes 𝑓: 0.39 (84887 hom.)
• Consequence: TMCC2 NM_014858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

Genes affected

TMCC2 (HGNC:24239): (transmembrane and coiled-coil domain family 2) Involved in amyloid precursor protein metabolic process. Located in 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=-0.31).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMCC2	NM_014858.4	c.748-11790T>C		intron_variant		ENST00000358024.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMCC2	ENST00000358024.8	c.748-11790T>C		intron_variant		1	NM_014858.4	P3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47976 AN: 151936 Hom.: 8606 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.390 AC: 421496 AN: 1080370 Hom.: 84887 Cov.: 33 AF XY: 0.390 AC XY: 199043 AN XY: 510128

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.316 AC: 47984 AN: 152054 Hom.: 8605 Cov.: 32 AF XY: 0.313 AC XY: 23279 AN XY: 74334

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.330

Alfa AF: 0.369 Hom.: 1338

Bravo AF: 0.296

Asia WGS AF: 0.135 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.79

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: rs1172113; hg19: chr1-205226288; COSMIC: COSV58002830; COSMIC: COSV58002830;