1-1535276-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001114748.2(TMEM240):c.*83C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,472,224 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00038 (3 hom.)
• Consequence: TMEM240 NM_001114748.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.244

Genes affected

TMEM240 (HGNC:25186): (transmembrane protein 240) This gene encodes a transmembrane-domain containing protein found in the brain and cerebellum. Mutations in this gene result in spinocerebellar ataxia 21. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-1535276-G-A is Benign according to our data. Variant chr1-1535276-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1702646.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00352 (534/151818) while in subpopulation AFR AF= 0.0123 (507/41374). AF 95% confidence interval is 0.0114. There are 3 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 535 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM240	NM_001114748.2	c.*83C>T		3_prime_UTR_variant	4/4	ENST00000378733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM240	ENST00000378733.9	c.*83C>T		3_prime_UTR_variant	4/4	2	NM_001114748.2	P1

Frequencies

GnomAD3 genomes AF: 0.00353 AC: 535 AN: 151706 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000383 AC: 506 AN: 1320406 Hom.: 3 Cov.: 27 AF XY: 0.000385 AC XY: 249 AN XY: 646898

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.000812

Gnomad4 ASJ exome AF: 0.0000927

Gnomad4 EAS exome AF: 0.0000299

Gnomad4 SAS exome AF: 0.000663

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000155

Gnomad4 OTH exome AF: 0.00110

GnomAD4 genome AF: 0.00352 AC: 534 AN: 151818 Hom.: 3 Cov.: 31 AF XY: 0.00336 AC XY: 249 AN XY: 74180

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.000916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000628

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000589

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00243 Hom.: 0

Bravo AF: 0.00406

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2022

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	12
Dann	Benign	0.66

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: rs574856684; hg19: chr1-1470656;