X-110003989-C-T

Variant names:

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

Variant summary

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

The NM_001353850.2(TMEM164):​c.-167C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,217 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: TMEM164 NM_001353850.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03499335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353850.2. 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>T	p.Pro72Leu	missense	Exon 2 of 7	NP_115603.2	Q5U3C3-1
	TMEM164	NM_001353850.2		c.-167C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	NP_001340779.1
	TMEM164	NM_001353851.2		c.-167C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001340780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM164	ENST00000372068.7	TSL:1 MANE Select	c.215C>T	p.Pro72Leu	missense	Exon 2 of 7	ENSP00000361138.2	Q5U3C3-1
	TMEM164	ENST00000372073.5	TSL:5	c.215C>T	p.Pro72Leu	missense	Exon 2 of 7	ENSP00000361143.1	Q5U3C3-1
	TMEM164	ENST00000464177.2	TSL:5	c.215C>T	p.Pro72Leu	missense	Exon 2 of 8	ENSP00000520920.1	Q5U3C3-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183192 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098217 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363577

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35204

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

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

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842126

Other (OTH) AF: 0.00 AC: 0 AN: 46094

GnomAD4 genome Cov.: 22

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
DANN	Benign	0.64
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.010
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.049
Sift	Benign	0.080	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.035
MutPred		0.22		Loss of relative solvent accessibility (P = 0.008)
MVP		0.082
MPC		0.96
ClinPred		0.031	T
GERP RS		-3.7
Varity_R		0.067
gMVP		0.80
Mutation Taster		=93/7	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: rs768316088; hg19: chrX-109247217;