chr1-205268009-T-C

Variant names:

• chr1-205268009-T-C
• rs1668871
• NM_014858.4:c.748-941T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014858.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC2	NM_014858.4	MANE Select	c.748-941T>C		intron	N/A	NP_055673.2
	TMCC2	NM_001242925.2		c.514-941T>C		intron	N/A	NP_001229854.1
	TMCC2	NM_001375651.1		c.514-941T>C		intron	N/A	NP_001362580.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMCC2	ENST00000358024.8	TSL:1 MANE Select	c.748-941T>C		intron	N/A	ENSP00000350718.3
	TMCC2	ENST00000330675.12	TSL:1	c.163-941T>C		intron	N/A	ENSP00000331842.7
	TMCC2	ENST00000637895.1	TSL:1	c.73-941T>C		intron	N/A	ENSP00000490308.1

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

African (AFR) AF: 0.162 AC: 2558 AN: 15784

American (AMR) AF: 0.248 AC: 244 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1710 AN: 5152

East Asian (EAS) AF: 0.105 AC: 380 AN: 3630

South Asian (SAS) AF: 0.143 AC: 2351 AN: 16460

European-Finnish (FIN) AF: 0.380 AC: 105 AN: 276

Middle Eastern (MID) AF: 0.244 AC: 396 AN: 1620

European-Non Finnish (NFE) AF: 0.386 AC: 294200 AN: 761812

Other (OTH) AF: 0.323 AC: 8829 AN: 27298

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

African (AFR) AF: 0.173 AC: 7169 AN: 41492

American (AMR) AF: 0.246 AC: 3760 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3472

East Asian (EAS) AF: 0.110 AC: 569 AN: 5166

South Asian (SAS) AF: 0.143 AC: 687 AN: 4816

European-Finnish (FIN) AF: 0.439 AC: 4625 AN: 10536

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25877 AN: 67944

Other (OTH) AF: 0.294 AC: 623 AN: 2116

Alfa AF: 0.346 Hom.: 32157

Bravo AF: 0.274

Asia WGS AF: 0.127 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.42
PhyloP100		0.045
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: rs1668871; hg19: chr1-205237137;