rs1353622545

Variant names:

• chrX-110067378-G-C
• rs1353622545
• NM_032227.4:c.422G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032227.4(TMEM164):​c.422G>C​(p.Gly141Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G141V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: TMEM164 NM_032227.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16459039).

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.422G>C	p.Gly141Ala	missense	Exon 3 of 7	NP_115603.2	Q5U3C3-1
	TMEM164	NM_001353849.2		c.422G>C	p.Gly141Ala	missense	Exon 3 of 8	NP_001340778.1	Q5U3C3-1
	TMEM164	NM_001353850.2		c.41G>C	p.Gly14Ala	missense	Exon 3 of 8	NP_001340779.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM164	ENST00000372068.7	TSL:1 MANE Select	c.422G>C	p.Gly141Ala	missense	Exon 3 of 7	ENSP00000361138.2	Q5U3C3-1
	TMEM164	ENST00000372073.5	TSL:5	c.422G>C	p.Gly141Ala	missense	Exon 3 of 7	ENSP00000361143.1	Q5U3C3-1
	TMEM164	ENST00000464177.2	TSL:5	c.422G>C	p.Gly141Ala	missense	Exon 3 of 8	ENSP00000520920.1	Q5U3C3-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183254 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097818 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 1 AN XY: 363224

African (AFR) AF: 0.00 AC: 0 AN: 26381

American (AMR) AF: 0.00 AC: 0 AN: 35181

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54129

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40499

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841823

Other (OTH) AF: 0.00 AC: 0 AN: 46086

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.077
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.49
DEOGEN2	Benign	0.021	T
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		2.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.054
Sift	Benign	0.78	T
Sift4G	Benign	0.78	T
Polyphen		0.0010	B
Vest4		0.53
MutPred		0.39		Loss of sheet (P = 0.007)
MVP		0.12
MPC		1.0
ClinPred		0.017	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.66
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs1353622545; hg19: chrX-109310606;