NM_001004313.3:c.445C>G

Variant names:

• chr17-10715491-G-C
• rs553428298
• NM_001004313.3:c.445C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004313.3(TMEM220):​c.445C>G​(p.Arg149Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,600,038 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.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: TMEM220 NM_001004313.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

Genes affected

TMEM220 (HGNC:33757): (transmembrane protein 220) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26568425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM220	NM_001004313.3	c.445C>G	p.Arg149Gly	missense_variant	Exon 6 of 6	ENST00000341871.8	NP_001004313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM220	ENST00000341871.8	c.445C>G	p.Arg149Gly	missense_variant	Exon 6 of 6	1	NM_001004313.3	ENSP00000339830.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000210 AC: 5 AN: 237762 Hom.: 0 AF XY: 0.0000233 AC XY: 3 AN XY: 128864

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 SAS exome AF: 0.000186

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1447816 Hom.: 0 Cov.: 30 AF XY: 0.00000417 AC XY: 3 AN XY: 719912

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000609

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74434

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.26	T;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.0	D;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.011	D;D;.
Sift4G	Uncertain	0.021	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.56
MutPred		0.36		Gain of glycosylation at S150 (P = 0.0449);.;.;
MVP		0.28
MPC		1.1
ClinPred		0.86	D
GERP RS		3.0
Varity_R		0.27
gMVP		0.78

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: rs553428298; hg19: chr17-10618808;