Genetic Variant LRRC34:p.Ser249Cys (chr3-169800667-T-A) – 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_001172779.2(LRRC34):c.745A>T(p.Ser249Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. S249G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC34
NM_001172779.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Publications

77 publications found

Variant links:

Genes affected

LRRC34 (HGNC:28408): (leucine rich repeat containing 34) Predicted to be involved in cell differentiation. Predicted to be located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

LRRC34 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=0.17169642).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172779.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC34	NM_001172779.2	MANE Select	c.745A>T	p.Ser249Cys	missense	Exon 7 of 11	NP_001166250.1	Q8IZ02-2
LRRC34	NM_001363888.2		c.562A>T	p.Ser188Cys	missense	Exon 7 of 11	NP_001350817.1	G3V115
LRRC34	NM_001370608.1		c.559A>T	p.Ser187Cys	missense	Exon 7 of 11	NP_001357537.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC34	ENST00000446859.7	TSL:2 MANE Select	c.745A>T	p.Ser249Cys	missense	Exon 7 of 11	ENSP00000414635.1	Q8IZ02-2
LRRC34	ENST00000522526.6	TSL:1	c.657+3386A>T		intron	N/A	ENSP00000429278.2	Q8IZ02-3
LRRC34	ENST00000895445.1		c.661A>T	p.Ser221Cys	missense	Exon 6 of 10	ENSP00000565504.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1375416

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679158

African (AFR)

AF:

0.00

AC:

AN:

31386

American (AMR)

AF:

0.00

AC:

AN:

35314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25114

East Asian (EAS)

AF:

0.00

AC:

AN:

35542

South Asian (SAS)

AF:

0.00

AC:

AN:

78534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5188

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072920

Other (OTH)

AF:

0.00

AC:

AN:

57548

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.27

M_CAP

Benign

0.033

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.77

PhyloP100

2.7

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.061

Sift

Benign

0.033

Sift4G

Benign

0.061

Polyphen

0.057

Vest4

0.28

MutPred

0.41

Loss of disorder (P = 0.0012)

MVP

0.49

MPC

0.30

ClinPred

0.74

GERP RS

3.4

Varity_R

0.17

gMVP

0.49

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over