rs1224329

Positions:

• chr6-37212461-G-A
• chr6-37212461-G-C

Variant summary

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

The NM_001395378.1(TMEM217B):​c.509C>T​(p.Ser170Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 447,330 control chromosomes in the GnomAD database, including 137,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (42402 hom., cov: 31)
  • Exomes 𝑓: 0.80 (95193 hom.)
• Consequence: TMEM217B NM_001395378.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.419

Genes affected

TMEM217B (HGNC:55922): (transmembrane protein 217B)

TMEM217 (HGNC:21238): (transmembrane protein 217) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM217 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM217B	NM_001395378.1	c.509C>T	p.Ser170Leu	missense_variant	2/2	ENST00000497775.2	NP_001382307.1
TMEM217	NM_001286401.2	c.*505C>T		3_prime_UTR_variant	3/3	ENST00000651039.2	NP_001273330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM217B	ENST00000497775.2	c.509C>T	p.Ser170Leu	missense_variant	2/2	2	NM_001395378.1	ENSP00000499172.1
TMEM217	ENST00000651039	c.*505C>T		3_prime_UTR_variant	3/3		NM_001286401.2	ENSP00000499204.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112429 AN: 151982 Hom.: 42383 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.735

GnomAD3 exomes AF: 0.803 AC: 104513 AN: 130218 Hom.: 42287 AF XY: 0.804 AC XY: 56761 AN XY: 70608

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.861

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.885

Gnomad SAS exome AF: 0.821

Gnomad FIN exome AF: 0.789

Gnomad NFE exome AF: 0.800

Gnomad OTH exome AF: 0.787

GnomAD4 exome AF: 0.801 AC: 236459 AN: 295230 Hom.: 95193 Cov.: 0 AF XY: 0.803 AC XY: 134895 AN XY: 167994

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.861

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.893

Gnomad4 SAS exome AF: 0.821

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.800

Gnomad4 OTH exome AF: 0.783

GnomAD4 genome AF: 0.740 AC: 112486 AN: 152100 Hom.: 42402 Cov.: 31 AF XY: 0.739 AC XY: 54935 AN XY: 74348

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.737

Alfa AF: 0.783 Hom.: 65371

Bravo AF: 0.732

Asia WGS AF: 0.825 AC: 2866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.55

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: rs1224329; hg19: chr6-37180237; COSMIC: COSV60824965; COSMIC: COSV60824965;