X-110003989-C-G

Variant names:

• chrX-110003989-C-G
• rs768316088
• NM_032227.4:c.215C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032227.4(TMEM164):​c.215C>G​(p.Pro72Arg) 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. 15/21 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: -0.0100
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03167498).
• BP6: Variant X-110003989-C-G is Benign according to our data. Variant chrX-110003989-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2569568.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032227.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM164	NM_032227.4	MANE Select	c.215C>G	p.Pro72Arg	missense	Exon 2 of 7	NP_115603.2	Q5U3C3-1
	TMEM164	NM_001353849.2		c.215C>G	p.Pro72Arg	missense	Exon 2 of 8	NP_001340778.1	Q5U3C3-1
	TMEM164	NM_001410717.1		c.215C>G	p.Pro72Arg	missense	Exon 2 of 6	NP_001397646.1	A1PI58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM164	ENST00000372068.7	TSL:1 MANE Select	c.215C>G	p.Pro72Arg	missense	Exon 2 of 7	ENSP00000361138.2	Q5U3C3-1
	TMEM164	ENST00000372073.5	TSL:5	c.215C>G	p.Pro72Arg	missense	Exon 2 of 7	ENSP00000361143.1	Q5U3C3-1
	TMEM164	ENST00000464177.2	TSL:5	c.215C>G	p.Pro72Arg	missense	Exon 2 of 8	ENSP00000520920.1	Q5U3C3-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.2
DANN	Benign	0.33
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.080	N
PhyloP100		-0.010
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.047
Sift	Benign	0.52	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.041
MutPred		0.20		Gain of MoRF binding (P = 0.0089)
MVP		0.068
MPC		1.0
ClinPred		0.019	T
GERP RS		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.77
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs768316088; hg19: chrX-109247217;