NM_001146197.3:c.20386G>A

Variant names:

• chr13-102730311-C-T
• rs146478877
• NM_001146197.3:c.20386G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001146197.3(LRTM3):​c.20386G>A​(p.Val6796Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,078 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. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V6796A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRTM3 NM_001146197.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028606832).
• BP6: Variant 13-102730311-C-T is Benign according to our data. Variant chr13-102730311-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3486293.Status of the report is criteria_provided_single_submitter, 1 stars.

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.20386G>A	p.Val6796Met	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.20386G>A	p.Val6796Met	missense	Exon 4 of 4	ENSP00000320232.3	Q8NDH2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399078 Hom.: 0 Cov.: 33 AF XY: 0.00000435 AC XY: 3 AN XY: 690048

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078882

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.086
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.042
DANN	Benign	0.69
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0071	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.6
PrimateAI	Benign	0.27	T
REVEL	Benign	0.020
Sift4G	Benign	0.17	T
Vest4		0.13
MVP		0.040
ClinPred		0.030	T
GERP RS		-5.0
gMVP		0.024
Mutation Taster		=99/1	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: rs146478877; hg19: chr13-103382661;