rs1668871

Positions:

• chr1-205268009-T-C
• chr1-205268009-T-G

Variant summary

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

The NM_014858.4(TMCC2):​c.748-941T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 985,034 control chromosomes in the GnomAD database, including 66,782 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 0.29 (7510 hom., cov: 32)
  • Exomes 𝑓: 0.37 (59272 hom.)
• Consequence: TMCC2 NM_014858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCC2	NM_014858.4	c.748-941T>C		intron_variant		ENST00000358024.8	NP_055673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMCC2	ENST00000358024.8	c.748-941T>C		intron_variant		1	NM_014858.4	ENSP00000350718	P3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44733 AN: 151900 Hom.: 7509 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.373 AC: 310773 AN: 833016 Hom.: 59272 Cov.: 34 AF XY: 0.373 AC XY: 143461 AN XY: 384672

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.294 AC: 44742 AN: 152018 Hom.: 7510 Cov.: 32 AF XY: 0.292 AC XY: 21709 AN XY: 74298

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.294

Alfa AF: 0.352 Hom.: 12863

Bravo AF: 0.274

Asia WGS AF: 0.127 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.42

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: rs1668871; hg19: chr1-205237137;