NM_001123376.3:c.413C>A

Variant names:

• chr10-44934719-C-A
• rs587777896
• NM_001123376.3:c.413C>A

Variant summary

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

The NM_001123376.3(TMEM72):​c.413C>A​(p.Ala138Asp) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM72 NM_001123376.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.06
• Publications: 0 publications found

Genes affected

TMEM72 (HGNC:31658): (transmembrane protein 72) This gene encodes a transmembrane protein which may be expressed specifically in the kidney. [provided by RefSeq, Sep 2016]

TMEM72-AS1 (HGNC:27349): (TMEM72 antisense RNA 1)

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=0.07229194).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123376.3. 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
	TMEM72	NM_001123376.3	MANE Select	c.413C>A	p.Ala138Asp	missense	Exon 5 of 5	NP_001116848.1	A0PK05-1
	TMEM72	NM_001345926.2		c.59C>A	p.Ala20Asp	missense	Exon 4 of 4	NP_001332855.1	A0PK05-2
	TMEM72-AS1	NR_033842.1		n.99-11493G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM72	ENST00000389583.5	TSL:1 MANE Select	c.413C>A	p.Ala138Asp	missense	Exon 5 of 5	ENSP00000374234.4	A0PK05-1
	TMEM72	ENST00000544540.5	TSL:1	c.59C>A	p.Ala20Asp	missense	Exon 4 of 4	ENSP00000439911.1	A0PK05-2
	TMEM72	ENST00000460364.1	TSL:2	n.424C>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.063
Sift	Benign	0.22	T
Sift4G	Benign	0.15	T
Polyphen		0.28	B
Vest4		0.20
MutPred		0.19		Loss of MoRF binding (P = 0.0391)
MVP		0.081
MPC		0.25
ClinPred		0.68	D
GERP RS		4.3
Varity_R		0.11
Mutation Taster		=86/14	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587777896; hg19: chr10-45430167;