rs719676

Positions:

• chr1-42788437-A-G
• chr1-42788437-A-T

Variant summary

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

The NM_001354602.2(TMEM269):​c.-98-1359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,084 control chromosomes in the GnomAD database, including 3,343 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 0.19 (3343 hom., cov: 32)
• Consequence: TMEM269 NM_001354602.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

Genes affected

TMEM269 (HGNC:52381): (transmembrane protein 269) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC107984946 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM269	NM_001354602.2	c.-98-1359A>G		intron_variant		ENST00000637012.2	NP_001341531.2
LOC107984946	XR_007066036.1	n.350T>C		non_coding_transcript_exon_variant	2/2
LOC107984946	XR_001738020.2	n.504T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM269	ENST00000637012.2	c.-98-1359A>G		intron_variant		5	NM_001354602.2	ENSP00000490213	P1
TMEM269	ENST00000536543.6	c.-292+373A>G		intron_variant		5		ENSP00000490716	P1
TMEM269	ENST00000421630.6	c.-98-1359A>G		intron_variant, NMD_transcript_variant		5		ENSP00000490287

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28959 AN: 151966 Hom.: 3342 Cov.: 32

Gnomad AFR AF: 0.0986

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.190 AC: 28965 AN: 152084 Hom.: 3343 Cov.: 32 AF XY: 0.192 AC XY: 14295 AN XY: 74314

Gnomad4 AFR AF: 0.0984

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.205

Alfa AF: 0.222 Hom.: 8113

Bravo AF: 0.186

Asia WGS AF: 0.390 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs719676; hg19: chr1-43254108;