2-216090612-T-C

Position:

• chr2-216090612-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.-126-5226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,290 control chromosomes in the GnomAD database, including 64,699 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 0.92 (64699 hom., cov: 32)
• Consequence: TMEM169 NM_001142311.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM169	NM_001142311.2	c.-126-5226T>C		intron_variant		ENST00000437356.7	NP_001135783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM169	ENST00000437356.7	c.-126-5226T>C		intron_variant		1	NM_001142311.2	ENSP00000401305.2

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139979 AN: 152172 Hom.: 64641 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.920 AC: 140097 AN: 152290 Hom.: 64699 Cov.: 32 AF XY: 0.918 AC XY: 68335 AN XY: 74456

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.875

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.965

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.901

Alfa AF: 0.898 Hom.: 66689

Bravo AF: 0.922

Asia WGS AF: 0.788 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.84

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: rs828920; hg19: chr2-216955335;