chr3-119436903-T-C

Variant names:

• chr3-119436903-T-C
• NM_018266.3:c.1000A>G

Variant summary

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

The NM_018266.3(TMEM39A):​c.1000A>G​(p.Thr334Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM39A NM_018266.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

Genes affected

TMEM39A (HGNC:25600): (transmembrane protein 39A) Involved in negative regulation of autophagosome assembly; negative regulation of autophagosome maturation; and positive regulation of viral genome replication. Located in endoplasmic reticulum 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=0.23915735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018266.3. 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
	TMEM39A	NM_018266.3	MANE Select	c.1000A>G	p.Thr334Ala	missense	Exon 7 of 9	NP_060736.1	Q9NV64-1
	TMEM39A	NR_073506.2		n.1463A>G		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM39A	ENST00000319172.10	TSL:1 MANE Select	c.1000A>G	p.Thr334Ala	missense	Exon 7 of 9	ENSP00000326063.5	Q9NV64-1
	TMEM39A	ENST00000438581.6	TSL:1	n.*668A>G		non_coding_transcript_exon	Exon 8 of 10	ENSP00000402149.2	Q9NV64-2
	TMEM39A	ENST00000438581.6	TSL:1	n.*668A>G		3_prime_UTR	Exon 8 of 10	ENSP00000402149.2	Q9NV64-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.15
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		7.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.13
Sift	Benign	0.42	T
Sift4G	Benign	0.41	T
Polyphen		0.019	B
Vest4		0.55
MutPred		0.57		Loss of catalytic residue at T334 (P = 0.127)
MVP		0.068
MPC		0.39
ClinPred		0.55	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.47
Mutation Taster		=68/32	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

hg19: chr3-119155750;