X-110004040-G-A

Variant names:

• chrX-110004040-G-A
• NM_032227.4:c.266G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032227.4(TMEM164):​c.266G>A​(p.Ser89Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,208 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: TMEM164 NM_032227.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.47
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3138197).

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.266G>A	p.Ser89Asn	missense	Exon 2 of 7	NP_115603.2	Q5U3C3-1
	TMEM164	NM_001353849.2		c.266G>A	p.Ser89Asn	missense	Exon 2 of 8	NP_001340778.1	Q5U3C3-1
	TMEM164	NM_001410717.1		c.266G>A	p.Ser89Asn	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.266G>A	p.Ser89Asn	missense	Exon 2 of 7	ENSP00000361138.2	Q5U3C3-1
	TMEM164	ENST00000372073.5	TSL:5	c.266G>A	p.Ser89Asn	missense	Exon 2 of 7	ENSP00000361143.1	Q5U3C3-1
	TMEM164	ENST00000464177.2	TSL:5	c.266G>A	p.Ser89Asn	missense	Exon 2 of 8	ENSP00000520920.1	Q5U3C3-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098208 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363576

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000237 AC: 2 AN: 842141

Other (OTH) AF: 0.00 AC: 0 AN: 46097

GnomAD4 genome Cov.: 22

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	0.24
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Benign	0.12	T
Sift4G	Benign	0.45	T
Polyphen		0.97	D
Vest4		0.47
MutPred		0.34		Loss of phosphorylation at S89 (P = 0.048)
MVP		0.40
MPC		1.0
ClinPred		0.79	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.96
Mutation Taster		=49/51	disease causing

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

hg19: chrX-109247268;