1-1535389-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.492C>T(p.His164=) variant causes a synonymous change. The variant allele was found at a frequency of 0.001 in 1,549,902 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00055 (7 hom.)
• Consequence: TMEM240 NM_001114748.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.60

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=-0.61).
• BP6: Variant 1-1535389-G-A is Benign according to our data. Variant chr1-1535389-G-A is described in ClinVar as [Benign]. Clinvar id is 711681.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-1535389-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0052 (791/152160) while in subpopulation AFR AF= 0.0178 (740/41522). AF 95% confidence interval is 0.0168. There are 6 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 787 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM240	NM_001114748.2	c.492C>T	p.His164=	synonymous_variant	4/4	ENST00000378733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM240	ENST00000378733.9	c.492C>T	p.His164=	synonymous_variant	4/4	2	NM_001114748.2	P1

Frequencies

GnomAD3 genomes AF: 0.00518 AC: 787 AN: 152046 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00115 AC: 172 AN: 149168 Hom.: 0 AF XY: 0.000881 AC XY: 70 AN XY: 79470

Gnomad AFR exome AF: 0.0189

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000184

Gnomad OTH exome AF: 0.000707

GnomAD4 exome AF: 0.000546 AC: 763 AN: 1397742 Hom.: 7 Cov.: 33 AF XY: 0.000480 AC XY: 331 AN XY: 689430

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000884

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000464

Gnomad4 OTH exome AF: 0.00126

GnomAD4 genome AF: 0.00520 AC: 791 AN: 152160 Hom.: 6 Cov.: 31 AF XY: 0.00496 AC XY: 369 AN XY: 74380

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00398 Hom.: 1

Bravo AF: 0.00595

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 15, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	11
Dann	Benign	0.94

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: rs375367099; hg19: chr1-1470769;