chr2-46480615-C-T

Variant names:

• chr2-46480615-C-T
• rs547792479
• NM_001424184.1:c.328C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001424184.1(TMEM247):​c.328C>T​(p.Arg110Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,338,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: TMEM247 NM_001424184.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.330
• Publications: 0 publications found

Genes affected

TMEM247 (HGNC:42967): (transmembrane protein 247) Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284608 (HGNC:):

LINC02583 (HGNC:53812): (long intergenic non-protein coding RNA 2583)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424184.1. 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
	TMEM247	NM_001424184.1	MANE Select	c.328C>T	p.Arg110Cys	missense	Exon 2 of 3	NP_001411113.1	A6NEH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM247	ENST00000434431.2	TSL:5 MANE Select	c.328C>T	p.Arg110Cys	missense	Exon 2 of 3	ENSP00000388684.1	A6NEH6
	ENSG00000284608	ENST00000432241.5	TSL:3	n.365-3629C>T		intron	N/A
	ENSG00000253515	ENST00000517716.3	TSL:5	n.114-19116C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 155480 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000299 AC: 4 AN: 1338868 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 659330

African (AFR) AF: 0.00 AC: 0 AN: 30740

American (AMR) AF: 0.00 AC: 0 AN: 33252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23126

East Asian (EAS) AF: 0.00 AC: 0 AN: 27786

South Asian (SAS) AF: 0.00 AC: 0 AN: 78682

European-Finnish (FIN) AF: 0.0000228 AC: 1 AN: 43900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5394

European-Non Finnish (NFE) AF: 9.60e-7 AC: 1 AN: 1041856

Other (OTH) AF: 0.0000369 AC: 2 AN: 54132

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.33
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
MutPred		0.24		Loss of MoRF binding (P = 0.0078)
MVP		0.27
ClinPred		0.92	D
GERP RS		2.7
Varity_R		0.090

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: rs547792479; hg19: chr2-46707754; COSMIC: COSV71363741;