rs772620209

Variant names:

• chr2-46480759-C-A
• rs772620209
• ENST00000434431.2:c.472C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-46480759-C-A
• chr2-46480759-C-G
• chr2-46480759-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001424184.1(TMEM247):​c.472C>A​(p.Arg158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000944 in 1,059,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: TMEM247 NM_001424184.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13372254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM247	NM_001424184.1	c.472C>A	p.Arg158Ser	missense_variant	Exon 2 of 3		NP_001411113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM247	ENST00000434431.2	c.472C>A	p.Arg158Ser	missense_variant	Exon 2 of 3	5		ENSP00000388684.1
ENSG00000284608	ENST00000432241.5	n.365-3485C>A		intron_variant	Intron 4 of 4	3
ENSG00000253515	ENST00000517716.2	n.80-18972C>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 9.44e-7 AC: 1 AN: 1059658 Hom.: 0 Cov.: 36 AF XY: 0.00000197 AC XY: 1 AN XY: 507554

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000949

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.59
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.14
Sift	Uncertain	0.018	D
Sift4G	Benign	0.18	T
Polyphen		0.49	P
MutPred		0.21		Gain of disorder (P = 0.0498);
MVP		0.030
ClinPred		0.52	D
GERP RS		3.9
Varity_R		0.089

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: rs772620209; hg19: chr2-46707898;