17-10723277-A-C

Variant names:

• chr17-10723277-A-C
• NM_001004313.3:c.340T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004313.3(TMEM220):​c.340T>G​(p.Ser114Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM220 NM_001004313.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18395314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM220	NM_001004313.3	c.340T>G	p.Ser114Ala	missense_variant	Exon 5 of 6	ENST00000341871.8	NP_001004313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM220	ENST00000341871.8	c.340T>G	p.Ser114Ala	missense_variant	Exon 5 of 6	1	NM_001004313.3	ENSP00000339830.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.340T>G (p.S114A) alteration is located in exon 5 (coding exon 5) of the TMEM220 gene. This alteration results from a T to G substitution at nucleotide position 340, causing the serine (S) at amino acid position 114 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Benign	0.071
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		1.0	D;B
Vest4		0.36
MutPred		0.22		Loss of glycosylation at S114 (P = 0.0272);.;
MVP		0.11
MPC		0.74
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-10626594; COSMIC: COSV59378891;