Genetic Variant NM_001004313.3:c.373T>C (chr17-10715563-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001004313.3(TMEM220):c.373T>C(p.Leu125Leu) 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
NM_001004313.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0260

Variant links:

Genes affected

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

TMEM220 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
TMEM220	NM_001004313.3 link	c.373T>C	p.Leu125Leu	synonymous_variant	Exon 6 of 6	ENST00000341871.8	NP_001004313.1	Q6QAJ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM220	ENST00000341871.8 link	c.373T>C	p.Leu125Leu	synonymous_variant	Exon 6 of 6	1	NM_001004313.3	ENSP00000339830.4		Q6QAJ8-1

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

297

AN:

152240

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00199

AC XY:

248

AN XY:

124748

show subpopulations

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.:

Cov.:

AF XY:

0.00249

AC XY:

1784

AN XY:

716676

show subpopulations

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.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74508

show subpopulations

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.:

Bravo

AF:

0.00177

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over