NM_178545.4:c.143C>A

Variant names:

• chr1-1918920-G-T
• rs772799278
• NM_178545.4:c.143C>A

Variant summary

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

The NM_178545.4(TMEM52):​c.143C>A​(p.Ala48Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,239,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A48V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: TMEM52 NM_178545.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

Genes affected

TMEM52 (HGNC:27916): (transmembrane protein 52) 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=0.24061802).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178545.4. 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
	TMEM52	NM_178545.4	MANE Select	c.143C>A	p.Ala48Asp	missense	Exon 3 of 5	NP_848640.1	Q8NDY8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM52	ENST00000310991.8	TSL:1 MANE Select	c.143C>A	p.Ala48Asp	missense	Exon 3 of 5	ENSP00000311122.3	Q8NDY8-1
	TMEM52	ENST00000902364.1		c.161C>A	p.Ala54Asp	missense	Exon 3 of 5	ENSP00000572423.1
	TMEM52	ENST00000378598.4	TSL:5	c.229C>A	p.Pro77Thr	missense	Exon 2 of 3	ENSP00000367861.3	B1AKR2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000323 AC: 4 AN: 1239358 Hom.: 0 Cov.: 31 AF XY: 0.00000166 AC XY: 1 AN XY: 600688

African (AFR) AF: 0.00 AC: 0 AN: 24098

American (AMR) AF: 0.00 AC: 0 AN: 12914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17514

East Asian (EAS) AF: 0.00 AC: 0 AN: 29562

South Asian (SAS) AF: 0.00 AC: 0 AN: 54822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3598

European-Non Finnish (NFE) AF: 0.00000394 AC: 4 AN: 1015838

Other (OTH) AF: 0.00 AC: 0 AN: 51188

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0083	T
Eigen	Benign	0.097
Eigen_PC	Benign	0.093
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.21
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.28		Gain of disorder (P = 0.0379)
MVP		0.24
MPC		4.3
ClinPred		0.87	D
GERP RS		2.3
PromoterAI		-0.025	Neutral
Varity_R		0.46
gMVP		0.28
Mutation Taster		=77/23	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: rs772799278; hg19: chr1-1850359;