Genetic Variant LRRC37A2:p.Ser102Leu (chr17-46513017-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001006607.3(LRRC37A2):c.305C>T(p.Ser102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 13)

Exomes 𝑓: 0.000089 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC37A2
NM_001006607.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.308

Publications

0 publications found

Variant links:

Genes affected

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

ARL17A (HGNC:24096): (ADP ribosylation factor like GTPase 17A) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026790768).

BP6

Variant 17-46513017-C-T is Benign according to our data. Variant chr17-46513017-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2595820.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC37A2	NM_001006607.3	MANE Select	c.305C>T	p.Ser102Leu	missense	Exon 1 of 14	NP_001006608.2	A6NM11
LRRC37A2	NM_001385803.1		c.305C>T	p.Ser102Leu	missense	Exon 1 of 14	NP_001372732.1
ARL17A	NM_001288812.1		c.*21+4077G>A		intron	N/A	NP_001275741.1	Q8IVW1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC37A2	ENST00000576629.6	TSL:5 MANE Select	c.305C>T	p.Ser102Leu	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
LRRC37A2	ENST00000706058.1		c.305C>T	p.Ser102Leu	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
LRRC37A2	ENST00000705813.1		c.-89+1409C>T		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes

AF:

0.000166

AC:

AN:

78322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000270

Gnomad SAS

AF:

0.00115

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000189

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000189

AC:

AN:

31792

AF XY:

0.000191

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000456

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000888

AC:

AN:

664062

Hom.:

Cov.:

AF XY:

0.0000884

AC XY:

AN XY:

328190

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000109

AC:

AN:

27638

American (AMR)

AF:

0.00

AC:

AN:

31694

Ashkenazi Jewish (ASJ)

AF:

0.000100

AC:

AN:

9952

East Asian (EAS)

AF:

0.000315

AC:

AN:

34902

South Asian (SAS)

AF:

0.0000835

AC:

AN:

35936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1426

European-Non Finnish (NFE)

AF:

0.0000848

AC:

AN:

459726

Other (OTH)

AF:

0.0000684

AC:

AN:

29248

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000166

AC:

AN:

78322

Hom.:

Cov.:

AF XY:

0.0000259

AC XY:

AN XY:

38568

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000165

AC:

AN:

30258

American (AMR)

AF:

0.00

AC:

AN:

7692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1224

East Asian (EAS)

AF:

0.000270

AC:

AN:

3708

South Asian (SAS)

AF:

0.00115

AC:

AN:

1746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000189

AC:

AN:

26424

Other (OTH)

AF:

0.00

AC:

AN:

832

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000252227), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.360

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000169

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.25

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.00065

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00021

LIST_S2

Benign

0.66

M_CAP

Benign

0.0015

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.31

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.6

REVEL

Benign

0.041

Sift

Benign

0.46

Sift4G

Benign

0.34

Polyphen

0.015

Vest4

0.14

MutPred

0.19

Loss of glycosylation at S102 (P = 0.0127)

MVP

0.030

ClinPred

0.010

GERP RS

-0.26

Varity_R

0.034

gMVP

0.024

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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