17-10715538-A-T

Variant names:

• chr17-10715538-A-T
• NM_001004313.3:c.398T>A

Variant summary

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

The NM_001004313.3(TMEM220):​c.398T>A​(p.Leu133His) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,166 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TMEM220 NM_001004313.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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 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
TMEM220	NM_001004313.3	c.398T>A	p.Leu133His	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.398T>A	p.Leu133His	missense_variant	Exon 6 of 6	1	NM_001004313.3	ENSP00000339830.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453166 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722762

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	25
DANN	Benign	0.71
DEOGEN2	Benign	0.19	T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.4	D;D;.
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.68
MutPred		0.36		Loss of stability (P = 0.0166);.;.;
MVP		0.35
MPC		1.3
ClinPred		0.85	D
GERP RS		6.2
Varity_R		0.48
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-10618855;