17-10715563-A-G

Position:

• chr17-10715563-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000341871.8(TMEM220):​c.373T>C​(p.Leu125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,593,854 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (12 hom.)
• Consequence: TMEM220 ENST00000341871.8 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0260

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-10715563-A-G is Benign according to our data. Variant chr17-10715563-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647483.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.026 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM220	NM_001004313.3	c.373T>C	p.Leu125=	synonymous_variant	6/6	ENST00000341871.8	NP_001004313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM220	ENST00000341871.8	c.373T>C	p.Leu125=	synonymous_variant	6/6	1	NM_001004313.3	ENSP00000339830	P1

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 297 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00341

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00196 AC: 450 AN: 229846 Hom.: 1 AF XY: 0.00199 AC XY: 248 AN XY: 124748

Gnomad AFR exome AF: 0.000319

Gnomad AMR exome AF: 0.000626

Gnomad ASJ exome AF: 0.000216

Gnomad EAS exome AF: 0.0000593

Gnomad SAS exome AF: 0.00127

Gnomad FIN exome AF: 0.000941

Gnomad NFE exome AF: 0.00336

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.00247 AC: 3557 AN: 1441496 Hom.: 12 Cov.: 30 AF XY: 0.00249 AC XY: 1784 AN XY: 716676

Gnomad4 AFR exome AF: 0.000308

Gnomad4 AMR exome AF: 0.000785

Gnomad4 ASJ exome AF: 0.000274

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.00107

Gnomad4 NFE exome AF: 0.00292

Gnomad4 OTH exome AF: 0.00193

GnomAD4 genome AF: 0.00195 AC: 297 AN: 152358 Hom.: 0 Cov.: 33 AF XY: 0.00161 AC XY: 120 AN XY: 74508

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00341

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00238 Hom.: 0

Bravo AF: 0.00177

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

TMEM220: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.55

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: rs147529920; hg19: chr17-10618880;