6-37212461-G-A

Variant names:

• chr6-37212461-G-A
• rs1224329
• NM_001395378.1:c.509C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395378.1. 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
	TMEM217B	NM_001395378.1	MANE Select	c.509C>T	p.Ser170Leu	missense	Exon 2 of 2	NP_001382307.1
	TMEM217	NM_001286401.2	MANE Select	c.*505C>T		3_prime_UTR	Exon 3 of 3	NP_001273330.1
	TMEM217B	NM_001395377.1		c.509C>T	p.Ser170Leu	missense	Exon 3 of 3	NP_001382306.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM217B	ENST00000497775.2	TSL:2 MANE Select	c.509C>T	p.Ser170Leu	missense	Exon 2 of 2	ENSP00000499172.1
	TMEM217	ENST00000651039.2	MANE Select	c.*505C>T		3_prime_UTR	Exon 3 of 3	ENSP00000499204.1
	TMEM217	ENST00000356757.7	TSL:1	c.*505C>T		3_prime_UTR	Exon 3 of 3	ENSP00000349198.2

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

GnomAD2 exomes AF: 0.803 AC: 104513 AN: 130218 AF XY: 0.804

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 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

African (AFR) AF: 0.587 AC: 4975 AN: 8482

American (AMR) AF: 0.861 AC: 22776 AN: 26456

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 6764 AN: 10004

East Asian (EAS) AF: 0.893 AC: 8134 AN: 9112

South Asian (SAS) AF: 0.821 AC: 47986 AN: 58442

European-Finnish (FIN) AF: 0.794 AC: 9885 AN: 12452

Middle Eastern (MID) AF: 0.802 AC: 2097 AN: 2616

European-Non Finnish (NFE) AF: 0.800 AC: 122963 AN: 153768

Other (OTH) AF: 0.783 AC: 10879 AN: 13898

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

African (AFR) AF: 0.583 AC: 24145 AN: 41444

American (AMR) AF: 0.788 AC: 12031 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2361 AN: 3470

East Asian (EAS) AF: 0.889 AC: 4600 AN: 5176

South Asian (SAS) AF: 0.825 AC: 3977 AN: 4822

European-Finnish (FIN) AF: 0.779 AC: 8245 AN: 10586

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54539 AN: 68006

Other (OTH) AF: 0.737 AC: 1559 AN: 2114

Alfa AF: 0.778 Hom.: 135659

Bravo AF: 0.732

Asia WGS AF: 0.825 AC: 2866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.55
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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