11-61392630-G-T

Variant names:

• chr11-61392630-G-T
• rs7107543
• NM_001173990.3:c.-2G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000334888.10(TMEM216):​c.-2G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,535,262 control chromosomes in the GnomAD database, including 2,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (1429 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (1182 hom.)
• Consequence: TMEM216 ENST00000334888.10 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.83
• Publications: 3 publications found

Genes affected

TMEM216 (HGNC:25018): (transmembrane protein 216) This locus encodes a transmembrane domain-containing protein. Mutations at this locus have been associated with Meckel-Gruber Syndrome Type 2, and Joubert Syndrome 2, also known as Cerebello-oculorenal Syndrome 2. [provided by RefSeq, Aug 2010]

TMEM216 Gene-Disease associations (from GenCC):

• Joubert syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• orofaciodigital syndrome type 6

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-61392630-G-T is Benign according to our data. Variant chr11-61392630-G-T is described in ClinVar as Benign. ClinVar VariationId is 193188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334888.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM216	NM_001173990.3	MANE Select	c.-2G>T		5_prime_UTR	Exon 1 of 5	NP_001167461.1
	TMEM216	NM_001173991.3		c.-2G>T		5_prime_UTR	Exon 1 of 5	NP_001167462.1
	TMEM216	NM_016499.6		c.-199G>T		5_prime_UTR	Exon 1 of 5	NP_057583.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM216	ENST00000515837.7	TSL:2 MANE Select	c.-2G>T		5_prime_UTR	Exon 1 of 5	ENSP00000440638.1
	TMEM216	ENST00000334888.10	TSL:2	c.-2G>T		5_prime_UTR	Exon 1 of 5	ENSP00000334844.5
	TMEM216	ENST00000398979.7	TSL:1	c.-199G>T		5_prime_UTR	Exon 1 of 5	ENSP00000381950.3

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11223 AN: 152108 Hom.: 1415 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.0550

GnomAD2 exomes AF: 0.0157 AC: 2117 AN: 134498 AF XY: 0.0118

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000952

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00918

GnomAD4 exome AF: 0.00739 AC: 10223 AN: 1383034 Hom.: 1182 Cov.: 32 AF XY: 0.00637 AC XY: 4350 AN XY: 682482

African (AFR) AF: 0.264 AC: 8338 AN: 31562

American (AMR) AF: 0.0144 AC: 514 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35720

South Asian (SAS) AF: 0.000669 AC: 53 AN: 79216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33864

Middle Eastern (MID) AF: 0.00765 AC: 43 AN: 5624

European-Non Finnish (NFE) AF: 0.000182 AC: 196 AN: 1078336

Other (OTH) AF: 0.0186 AC: 1078 AN: 57854

GnomAD4 genome AF: 0.0741 AC: 11274 AN: 152228 Hom.: 1429 Cov.: 32 AF XY: 0.0719 AC XY: 5350 AN XY: 74434

African (AFR) AF: 0.257 AC: 10676 AN: 41508

American (AMR) AF: 0.0279 AC: 427 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68012

Other (OTH) AF: 0.0545 AC: 115 AN: 2112

Alfa AF: 0.0209 Hom.: 131

Bravo AF: 0.0834

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Joubert syndrome 2 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Joubert syndrome (1)
-	-	1	Meckel syndrome, type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		1.8
PromoterAI		-0.095	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7107543; hg19: chr11-61160102;