X-110173341-C-T

Variant names:

• chrX-110173341-C-T
• rs146630087
• NM_032227.4:c.784C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_032227.4(TMEM164):​c.784C>T​(p.Leu262Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,209,953 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L262V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000091 (0 hom. 3 hem.)
• Consequence: TMEM164 NM_032227.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26801962).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

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.784C>T	p.Leu262Phe	missense	Exon 7 of 7	NP_115603.2	Q5U3C3-1
	TMEM164	NM_001353849.2		c.784C>T	p.Leu262Phe	missense	Exon 7 of 8	NP_001340778.1	Q5U3C3-1
	TMEM164	NM_001410717.1		c.667C>T	p.Leu223Phe	missense	Exon 5 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.784C>T	p.Leu262Phe	missense	Exon 7 of 7	ENSP00000361138.2	Q5U3C3-1
	TMEM164	ENST00000372073.5	TSL:5	c.784C>T	p.Leu262Phe	missense	Exon 7 of 7	ENSP00000361143.1	Q5U3C3-1
	TMEM164	ENST00000464177.2	TSL:5	c.784C>T	p.Leu262Phe	missense	Exon 7 of 8	ENSP00000520920.1	Q5U3C3-1

Frequencies

GnomAD3 genomes AF: 0.00000894 AC: 1 AN: 111840 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183437 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000911 AC: 10 AN: 1098113 Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 3 AN XY: 363469

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 842011

Other (OTH) AF: 0.0000217 AC: 1 AN: 46091

GnomAD4 genome AF: 0.00000894 AC: 1 AN: 111840 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33992

African (AFR) AF: 0.00 AC: 0 AN: 30700

American (AMR) AF: 0.00 AC: 0 AN: 10623

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.00 AC: 0 AN: 2618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6085

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53160

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		0.084	B
Vest4		0.33
MutPred		0.39		Loss of helix (P = 0.0444)
MVP		0.78
MPC		1.2
ClinPred		0.33	T
GERP RS		5.2
Varity_R		0.38
gMVP		0.98
Mutation Taster		=58/42	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: rs146630087; hg19: chrX-109416569;