chr11-61362252-A-G

Position:

• chr11-61362252-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000542946.2(TMEM138):​c.-308A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 152,364 control chromosomes in the GnomAD database, including 435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (434 hom., cov: 33)
  • Exomes 𝑓: 0.050 (1 hom.)
• Consequence: TMEM138 ENST00000542946.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.46

Genes affected

TMEM138 (HGNC:26944): (transmembrane protein 138) This gene encodes a multi-pass transmembrane protein. Reduced expression of this gene in mouse fibroblasts causes short cilia and failure of ciliogenesis. Expression of this gene is tightly coordinated with expression of the neighboring gene TMEM216. Mutations in this gene are associated with the autosomal recessive neurodevelopmental disorder Joubert Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

CYB561A3 (HGNC:23014): (cytochrome b561 family member A3) Predicted to enable transmembrane ascorbate ferrireductase activity. Predicted to be involved in cellular iron ion homeostasis. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-61362252-A-G is Benign according to our data. Variant chr11-61362252-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 305050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYB561A3	NM_001161454.1	c.-749T>C		5_prime_UTR_variant	1/8
CYB561A3	XM_011544821.3	c.-749T>C		5_prime_UTR_variant	1/8
CYB561A3	XM_024448398.2	c.-749T>C		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM138	ENST00000542946.2	c.-308A>G		5_prime_UTR_variant	1/3	1
CYB561A3	ENST00000426130.6	c.-749T>C		5_prime_UTR_variant	1/8	5
TMEM138	ENST00000451389.7	c.-308A>G		5_prime_UTR_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6962 AN: 152186 Hom.: 428 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0544

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0500 AC: 3 AN: 60 Hom.: 1 Cov.: 0 AF XY: 0.0455 AC XY: 2 AN XY: 44

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0458 AC: 6980 AN: 152304 Hom.: 434 Cov.: 33 AF XY: 0.0457 AC XY: 3403 AN XY: 74482

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0536

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.00591

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0314 Hom.: 42

Bravo AF: 0.0492

Asia WGS AF: 0.0370 AC: 131 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial aplasia of the vermis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.38

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: rs7120780; hg19: chr11-61129724;