NM_152402.3:c.1077C>G

Variant names:

• chr4-117084317-G-C
• NM_152402.3:c.1077C>G

Variant summary

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

The NM_152402.3(TRAM1L1):​c.1077C>G​(p.Asp359Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D359A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAM1L1 NM_152402.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.141
• Publications: 0 publications found

Genes affected

TRAM1L1 (HGNC:28371): (translocation associated membrane protein 1 like 1) Predicted to be involved in protein insertion into ER membrane. Predicted to be integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105377388 (HGNC:):

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=0.15713823).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152402.3. 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
	TRAM1L1	NM_152402.3	MANE Select	c.1077C>G	p.Asp359Glu	missense	Exon 1 of 1	NP_689615.2	Q8N609

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAM1L1	ENST00000310754.5	TSL:6 MANE Select	c.1077C>G	p.Asp359Glu	missense	Exon 1 of 1	ENSP00000309402.4	Q8N609

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.14
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.15
Sift	Uncertain	0.017	D
Sift4G	Benign	0.44	T
Polyphen		1.0	D
Vest4		0.048
MutPred		0.14		Gain of glycosylation at P361 (P = 0.0954)
MVP		0.28
MPC		0.27
ClinPred		0.52	D
GERP RS		-1.4
Varity_R		0.076
gMVP		0.12
Mutation Taster		=84/16	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: chr4-118005473;