3-169800679-G-A

Variant names:

• chr3-169800679-G-A
• rs906722069
• NM_001172779.2:c.733C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001172779.2(LRRC34):​c.733C>T​(p.Pro245Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: LRRC34 NM_001172779.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.62
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

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.733C>T	p.Pro245Ser	missense	Exon 7 of 11	NP_001166250.1	Q8IZ02-2
	LRRC34	NM_001363888.2		c.550C>T	p.Pro184Ser	missense	Exon 7 of 11	NP_001350817.1	G3V115
	LRRC34	NM_001370608.1		c.547C>T	p.Pro183Ser	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.733C>T	p.Pro245Ser	missense	Exon 7 of 11	ENSP00000414635.1	Q8IZ02-2
	LRRC34	ENST00000522526.6	TSL:1	c.657+3374C>T		intron	N/A	ENSP00000429278.2	Q8IZ02-3
	LRRC34	ENST00000895445.1		c.649C>T	p.Pro217Ser	missense	Exon 6 of 10	ENSP00000565504.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74282

African (AFR) AF: 0.0000242 AC: 1 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.81	T
PhyloP100		7.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.28
Sift	Benign	0.089	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.62
MutPred		0.67		Loss of stability (P = 0.0341)
MVP		0.65
MPC		0.24
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.30
gMVP		0.58
Mutation Taster		=67/33	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

Other links and lift over

dbSNP: rs906722069; hg19: chr3-169518467;