NM_001004313.3:c.31G>A

Variant names:

• chr17-10729821-C-T
• rs1009320879
• NM_001004313.3:c.31G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004313.3(TMEM220):​c.31G>A​(p.Gly11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 1,396,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: TMEM220 NM_001004313.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.882
• Publications: 0 publications found

Genes affected

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

TMEM220-AS1 (HGNC:44357): (TMEM220 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107194155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004313.3. 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
	TMEM220	NM_001004313.3	MANE Select	c.31G>A	p.Gly11Arg	missense	Exon 1 of 6	NP_001004313.1	Q6QAJ8-1
	TMEM220	NM_001359647.2		c.31G>A	p.Gly11Arg	missense	Exon 1 of 6	NP_001346576.1
	TMEM220	NM_001330139.3		c.31G>A	p.Gly11Arg	missense	Exon 1 of 5	NP_001317068.1	Q6QAJ8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM220	ENST00000341871.8	TSL:1 MANE Select	c.31G>A	p.Gly11Arg	missense	Exon 1 of 6	ENSP00000339830.4	Q6QAJ8-1
	TMEM220	ENST00000455996.6	TSL:1	c.31G>A	p.Gly11Arg	missense	Exon 1 of 5	ENSP00000396973.2	Q6QAJ8-2
	TMEM220	ENST00000857803.1		c.31G>A	p.Gly11Arg	missense	Exon 1 of 7	ENSP00000527862.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151836 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000182 AC: 1 AN: 54866 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: 0.0000560

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000538 AC: 67 AN: 1244424 Hom.: 0 Cov.: 29 AF XY: 0.0000530 AC XY: 32 AN XY: 603944

African (AFR) AF: 0.0000385 AC: 1 AN: 25944

American (AMR) AF: 0.00 AC: 0 AN: 25408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20028

East Asian (EAS) AF: 0.00 AC: 0 AN: 28252

South Asian (SAS) AF: 0.00 AC: 0 AN: 61062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.0000631 AC: 63 AN: 998970

Other (OTH) AF: 0.0000589 AC: 3 AN: 50962

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151836 Hom.: 0 Cov.: 34 AF XY: 0.0000270 AC XY: 2 AN XY: 74188

African (AFR) AF: 0.0000243 AC: 1 AN: 41128

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000876 Hom.: 0

Bravo AF: 0.0000302

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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.88
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.074
Sift	Benign	0.30	T
Sift4G	Benign	0.34	T
Polyphen		0.77	P
Vest4		0.23
MutPred		0.49		Gain of MoRF binding (P = 9e-04)
MVP		0.22
MPC		0.69
ClinPred		0.17	T
GERP RS		-1.5
PromoterAI		0.0031	Neutral
Varity_R		0.11
gMVP		0.33
Mutation Taster		=98/2	polymorphism

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: rs1009320879; hg19: chr17-10633138;