3-169800679-G-T

Variant names:

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

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>A​(p.Pro245Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P245S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LRRC34 NM_001172779.2 missense
• Clinical Significance: Not reported in ClinVar
• 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, 0.838

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>A	p.Pro245Thr	missense	Exon 7 of 11	NP_001166250.1	Q8IZ02-2
	LRRC34	NM_001363888.2		c.550C>A	p.Pro184Thr	missense	Exon 7 of 11	NP_001350817.1	G3V115
	LRRC34	NM_001370608.1		c.547C>A	p.Pro183Thr	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>A	p.Pro245Thr	missense	Exon 7 of 11	ENSP00000414635.1	Q8IZ02-2
	LRRC34	ENST00000522526.6	TSL:1	c.657+3374C>A		intron	N/A	ENSP00000429278.2	Q8IZ02-3
	LRRC34	ENST00000895445.1		c.649C>A	p.Pro217Thr	missense	Exon 6 of 10	ENSP00000565504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000744 AC: 1 AN: 134354 AF XY: 0.0000137

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: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381460 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 681868

African (AFR) AF: 0.00 AC: 0 AN: 31546

American (AMR) AF: 0.00 AC: 0 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25152

East Asian (EAS) AF: 0.00 AC: 0 AN: 35612

South Asian (SAS) AF: 0.00 AC: 0 AN: 79144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5236

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077408

Other (OTH) AF: 0.00 AC: 0 AN: 57796

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.71	T
PhyloP100		7.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.69		Loss of stability (P = 0.0239)
MVP		0.65
MPC		0.39
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.41
gMVP		0.58
Mutation Taster		=64/36	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;