10-49184968-C-T

Position:

• chr10-49184968-C-T

Variant summary

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

The NM_001288740.3(TMEM273):​c.43+3326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,986 control chromosomes in the GnomAD database, including 8,652 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 (8652 hom., cov: 32)
• Consequence: TMEM273 NM_001288740.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

Genes affected

TMEM273 (HGNC:27274): (transmembrane protein 273) 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM273	NM_001288740.3	c.43+3326G>A		intron_variant		ENST00000374153.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM273	ENST00000374153.7	c.43+3326G>A		intron_variant		3	NM_001288740.3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50840 AN: 151868 Hom.: 8643 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.335 AC: 50875 AN: 151986 Hom.: 8652 Cov.: 32 AF XY: 0.340 AC XY: 25257 AN XY: 74278

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.343

Alfa AF: 0.348 Hom.: 19602

Bravo AF: 0.326

Asia WGS AF: 0.441 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.60

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: rs1962336; hg19: chr10-50393013;