6-37212461-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395378.1(TMEM217B):​c.509C>G​(p.Ser170*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: TMEM217B NM_001395378.1 stop_gained
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM217B	NM_001395378.1	c.509C>G	p.Ser170*	stop_gained	Exon 2 of 2	ENST00000497775.2	NP_001382307.1
TMEM217	NM_001286401.2	c.*505C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000651039.2	NP_001273330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM217B	ENST00000497775.2	c.509C>G	p.Ser170*	stop_gained	Exon 2 of 2	2	NM_001395378.1	ENSP00000499172.1
TMEM217	ENST00000651039	c.*505C>G		3_prime_UTR_variant	Exon 3 of 3		NM_001286401.2	ENSP00000499204.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Pathogenic	32
DANN	Benign	0.41

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;