rs828922

chr2-216091945-T-C

Variant summary

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

The NM_001142311.2(TMEM169):c.-126-3893T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,102 control chromosomes in the GnomAD database, including 4,950 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 0.23 (4950 hom., cov: 31)
• Consequence: TMEM169 NM_001142311.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

Genes affected

TMEM169 (HGNC:25130): (transmembrane protein 169) Predicted to be integral component of membrane. [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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM169	NM_001142311.2	c.-126-3893T>C		intron_variant		ENST00000437356.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM169	ENST00000437356.7	c.-126-3893T>C		intron_variant		1	NM_001142311.2	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34908 AN: 151984 Hom.: 4949 Cov.: 31

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34909 AN: 152102 Hom.: 4950 Cov.: 31 AF XY: 0.228 AC XY: 16916 AN XY: 74344

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0618

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.225

Alfa AF: 0.285 Hom.: 8970

Bravo AF: 0.207

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	13
Dann	Benign	0.89

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: rs828922; hg19: chr2-216956668;