3-169800665-A-T

Variant names:

• chr3-169800665-A-T
• NM_001172779.2:c.747T>A
• LRRC34 p.Ser249Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001172779.2(LRRC34):​c.747T>A​(p.Ser249Arg) 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. 14/21 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)
• Consequence: LRRC34 NM_001172779.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 0 publications found

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]

ACMG classification

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=0.0935244).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC34	NM_001172779.2	MANE Select	c.747T>A	p.Ser249Arg	missense	Exon 7 of 11	NP_001166250.1	Q8IZ02-2
	LRRC34	NM_001363888.2		c.564T>A	p.Ser188Arg	missense	Exon 7 of 11	NP_001350817.1	G3V115
	LRRC34	NM_001370608.1		c.561T>A	p.Ser187Arg	missense	Exon 7 of 11	NP_001357537.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC34	ENST00000446859.7	TSL:2 MANE Select	c.747T>A	p.Ser249Arg	missense	Exon 7 of 11	ENSP00000414635.1	Q8IZ02-2
	LRRC34	ENST00000522526.6	TSL:1	c.657+3388T>A		intron	N/A	ENSP00000429278.2	Q8IZ02-3
	LRRC34	ENST00000895445.1		c.663T>A	p.Ser221Arg	missense	Exon 6 of 10	ENSP00000565504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.8
DANN	Benign	0.96
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.88	T
PhyloP100		-0.10
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.065
Sift	Benign	0.033	D
Sift4G	Benign	0.12	T
Varity_R		0.31
gMVP		0.63
Mutation Taster		=98/2	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-169518453;