Genetic Variant LRRC31:p.Thr253Asn (chr3-169856401-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024727.4(LRRC31):c.758C>A(p.Thr253Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. T253I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LRRC31
NM_024727.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09

Publications

0 publications found

Variant links:

Genes affected

LRRC31 (HGNC:26261): (leucine rich repeat containing 31)

LRRC31 links:

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ACMG classification

Classification was made for transcript

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=0.24065971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024727.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC31	NM_024727.4	MANE Select	c.758C>A	p.Thr253Asn	missense	Exon 5 of 9	NP_079003.2	Q6UY01-1
LRRC31	NM_001277128.2		c.590C>A	p.Thr197Asn	missense	Exon 4 of 8	NP_001264057.1	Q6UY01-2
LRRC31	NM_001277127.2		c.758C>A	p.Thr253Asn	missense	Exon 5 of 9	NP_001264056.1	Q6UY01-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC31	ENST00000316428.10	TSL:1 MANE Select	c.758C>A	p.Thr253Asn	missense	Exon 5 of 9	ENSP00000325978.5	Q6UY01-1
LRRC31	ENST00000523069.1	TSL:1	c.758C>A	p.Thr253Asn	missense	Exon 5 of 9	ENSP00000429145.1	Q6UY01-4
LRRC31	ENST00000945890.1		c.734C>A	p.Thr245Asn	missense	Exon 5 of 9	ENSP00000615949.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

244916

AF XY:

0.00000752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454208

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33276

American (AMR)

AF:

0.00

AC:

AN:

43814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39040

South Asian (SAS)

AF:

0.00

AC:

AN:

84818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108340

Other (OTH)

AF:

0.00

AC:

AN:

60006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.016

Eigen

Benign

0.051

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.76

M_CAP

Benign

0.030

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.59

PhyloP100

3.1

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.12

Sift

Benign

0.29

Sift4G

Uncertain

0.034

Polyphen

0.98

Vest4

0.29

MutPred

0.33

Gain of loop (P = 0.0195)

MVP

0.63

MPC

0.17

ClinPred

0.45

GERP RS

4.8

Varity_R

0.12

gMVP

0.23

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over