X-110003985-A-G

Variant names:

• chrX-110003985-A-G
• NM_032227.4:c.211A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032227.4(TMEM164):​c.211A>G​(p.Ser71Gly) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TMEM164 NM_032227.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.680

Genes affected

TMEM164 (HGNC:26217): (transmembrane protein 164) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039225817).
• BP6: Variant X-110003985-A-G is Benign according to our data. Variant chrX-110003985-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2569567.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM164	NM_032227.4	c.211A>G	p.Ser71Gly	missense_variant	Exon 2 of 7	ENST00000372068.7	NP_115603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM164	ENST00000372068.7	c.211A>G	p.Ser71Gly	missense_variant	Exon 2 of 7	1	NM_032227.4	ENSP00000361138.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 07, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	13
DANN	Benign	0.64
DEOGEN2	Benign	0.019	T;T;.
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.53	.;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.40	N;N;N
REVEL	Benign	0.040
Sift	Benign	0.72	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.054
MutPred		0.19		Loss of phosphorylation at S71 (P = 0.0072);Loss of phosphorylation at S71 (P = 0.0072);Loss of phosphorylation at S71 (P = 0.0072);
MVP		0.068
MPC		0.87
ClinPred		0.036	T
GERP RS		0.26
Varity_R		0.049
gMVP		0.59

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: chrX-109247213;