rs323720

Variant names:

• chr1-42805362-T-C
• rs323720
• ENST00000421630.6:n.*121-23T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-42805362-T-C
• chr1-42805362-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000421630.6(TMEM269):​n.*121-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,110 control chromosomes in the GnomAD database, including 8,910 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 0.33 (8903 hom., cov: 32)
  • Exomes 𝑓: 0.43 (7 hom.)
• Consequence: TMEM269 ENST00000421630.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 21 publications found

Genes affected

TMEM269 (HGNC:52381): (transmembrane protein 269) Predicted to be integral component of membrane. [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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM269	ENST00000421630.6	n.*121-23T>C		intron_variant	Intron 7 of 10	5		ENSP00000490287.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50560 AN: 151924 Hom.: 8883 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.426 AC: 29 AN: 68 Hom.: 7 Cov.: 0 AF XY: 0.325 AC XY: 13 AN XY: 40

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.444 AC: 8 AN: 18

European-Non Finnish (NFE) AF: 0.476 AC: 20 AN: 42

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.333 AC: 50620 AN: 152042 Hom.: 8903 Cov.: 32 AF XY: 0.332 AC XY: 24678 AN XY: 74306

African (AFR) AF: 0.405 AC: 16796 AN: 41440

American (AMR) AF: 0.304 AC: 4643 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.0154 AC: 80 AN: 5190

South Asian (SAS) AF: 0.274 AC: 1320 AN: 4818

European-Finnish (FIN) AF: 0.380 AC: 4016 AN: 10574

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21758 AN: 67962

Other (OTH) AF: 0.311 AC: 656 AN: 2108

Alfa AF: 0.317 Hom.: 33264

Bravo AF: 0.329

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		-0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs323720; hg19: chr1-43271033;