NM_001286401.2:c.471G>T

Variant names:

• chr6-37218560-C-A
• rs141081292
• NM_001286401.2:c.471G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001286401.2(TMEM217):​c.471G>T​(p.Arg157Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R157R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TMEM217 NM_001286401.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.72 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286401.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM217	NM_001286401.2	MANE Select	c.471G>T	p.Arg157Arg	synonymous	Exon 2 of 3	NP_001273330.1	Q8N7C4-2
	TMEM217B	NM_001395378.1	MANE Select	c.-27-5564G>T		intron	N/A	NP_001382307.1	A0A494BZU4
	TMEM217	NM_145316.4		c.471G>T	p.Arg157Arg	synonymous	Exon 2 of 4	NP_660359.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM217	ENST00000651039.2	MANE Select	c.471G>T	p.Arg157Arg	synonymous	Exon 2 of 3	ENSP00000499204.1	Q8N7C4-2
	TMEM217	ENST00000356757.7	TSL:1	c.471G>T	p.Arg157Arg	synonymous	Exon 2 of 3	ENSP00000349198.2	Q8N7C4-2
	TMEM217	ENST00000357219.4	TSL:1	c.471G>T	p.Arg157Arg	synonymous	Exon 2 of 2	ENSP00000498422.1	A0A494C081

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.37
PhyloP100		-1.7
PromoterAI		-0.0090	Neutral

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: rs141081292; hg19: chr6-37186336;