rs3097418

chr8-93770503-G-A

Variant summary

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

The NM_153704.6(TMEM67):c.652-2086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,034 control chromosomes in the GnomAD database, including 5,137 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 0.26 (5137 hom., cov: 32)
• Consequence: TMEM67 NM_153704.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

Genes affected

TMEM67 (HGNC:28396): (transmembrane protein 67) The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Meckel syndrome type 3 (MKS3) and Joubert syndrome type 6 (JBTS6). [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM67	NM_153704.6	c.652-2086G>A		intron_variant		ENST00000453321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM67	ENST00000453321.8	c.652-2086G>A		intron_variant		1	NM_153704.6	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38729 AN: 151916 Hom.: 5124 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.255 AC: 38773 AN: 152034 Hom.: 5137 Cov.: 32 AF XY: 0.256 AC XY: 18996 AN XY: 74312

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.263

Alfa AF: 0.279 Hom.: 3426

Bravo AF: 0.250

Asia WGS AF: 0.283 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.7
Dann	Benign	0.67

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: rs3097418; hg19: chr8-94782731;