13-102730133-G-T

Variant names:

• chr13-102730133-G-T
• rs184806294
• NM_001146197.3:c.20564C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146197.3(LRTM3):​c.20564C>A​(p.Thr6855Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 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. T6855I) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: LRTM3 NM_001146197.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271
• Publications: 1 publications found

Genes affected

LRTM3 (HGNC:26851): (coiled-coil domain containing 168)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049661428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146197.3. 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
	LRTM3	NM_001146197.3	MANE Select	c.20564C>A	p.Thr6855Lys	missense	Exon 4 of 4	NP_001139669.1	Q8NDH2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC168	ENST00000322527.4	TSL:3 MANE Select	c.20564C>A	p.Thr6855Lys	missense	Exon 4 of 4	ENSP00000320232.3	Q8NDH2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152292 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.2
DANN	Benign	0.95
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.052	N
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.27
PrimateAI	Benign	0.32	T
REVEL	Benign	0.017
Sift4G	Pathogenic	0.0	D
Vest4		0.19
MVP		0.014
ClinPred		0.31	T
GERP RS		1.3
gMVP		0.046
Mutation Taster		=100/0	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

dbSNP: rs184806294; hg19: chr13-103382483;