chr4-117085215-G-A

Variant names:

• chr4-117085215-G-A
• rs375695919
• NM_152402.3:c.179C>T

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.179C>T​(p.Pro60Leu) 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. 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. P60H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAM1L1 NM_152402.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• 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=0.15178585).

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.179C>T	p.Pro60Leu	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.179C>T	p.Pro60Leu	missense	Exon 1 of 1	ENSP00000309402.4	Q8N609

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.98
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.069
Sift	Benign	0.070	T
Sift4G	Benign	0.32	T
Polyphen		0.24	B
Vest4		0.074
MutPred		0.48		Gain of sheet (P = 0.0028)
MVP		0.40
MPC		0.26
ClinPred		0.30	T
GERP RS		3.4
PromoterAI		-0.0042	Neutral
Varity_R		0.064
gMVP		0.49
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs375695919; hg19: chr4-118006371;