Genetic Variant NM_001146197.3:c.20387T>C (chr13-102730310-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001146197.3(LRTM3):c.20387T>C(p.Val6796Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 1,551,386 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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. V6796M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0054 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 58 hom. )

Consequence

LRTM3
NM_001146197.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.75

Publications

7 publications found

Variant links:

Genes affected

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

LRTM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034114122).

BP6

Variant 13-102730310-A-G is Benign according to our data. Variant chr13-102730310-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2643903.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 58 AR gene

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.20387T>C	p.Val6796Ala	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.20387T>C	p.Val6796Ala	missense	Exon 4 of 4	ENSP00000320232.3	Q8NDH2

Frequencies

GnomAD3 genomes

AF:

0.00537

AC:

817

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00773

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00885

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00448

AC:

696

AN:

155290

AF XY:

0.00432

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.00405

Gnomad ASJ exome

AF:

0.00567

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000360

Gnomad NFE exome

AF:

0.00852

Gnomad OTH exome

AF:

0.00435

GnomAD4 exome

AF:

0.00773

AC:

10816

AN:

1399086

Hom.:

Cov.:

AF XY:

0.00753

AC XY:

5194

AN XY:

690052

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

31588

American (AMR)

AF:

0.00417

AC:

149

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

138

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35726

South Asian (SAS)

AF:

0.000240

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.000611

AC:

AN:

49082

Middle Eastern (MID)

AF:

0.00334

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00930

AC:

10029

AN:

1078882

Other (OTH)

AF:

0.00662

AC:

384

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

613

1226

1838

2451

3064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00536

AC:

816

AN:

152300

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

367

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41572

American (AMR)

AF:

0.00772

AC:

118

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00883

AC:

601

AN:

68028

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00723

Hom.:

Bravo

AF:

0.00610

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00324

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.045

M_CAP

Benign

0.012

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.97

PhyloP100

1.7

PrimateAI

Benign

0.28

REVEL

Benign

0.038

Sift4G

Uncertain

0.0060

Vest4

0.14

MVP

0.040

ClinPred

0.013

GERP RS

2.7

gMVP

0.031

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over