3-169804064-C-T

Variant names:

• chr3-169804064-C-T
• rs746708653
• NM_001172779.2:c.646G>A

Variant summary

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

The NM_001172779.2(LRRC34):​c.646G>A​(p.Asp216Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000279 in 1,435,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: LRRC34 NM_001172779.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.646G>A	p.Asp216Asn	missense	Exon 6 of 11	NP_001166250.1	Q8IZ02-2
	LRRC34	NM_153353.5		c.646G>A	p.Asp216Asn	missense	Exon 6 of 10	NP_699184.2	Q8IZ02-3
	LRRC34	NM_001363888.2		c.463G>A	p.Asp155Asn	missense	Exon 6 of 11	NP_001350817.1	G3V115

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC34	ENST00000446859.7	TSL:2 MANE Select	c.646G>A	p.Asp216Asn	missense	Exon 6 of 11	ENSP00000414635.1	Q8IZ02-2
	LRRC34	ENST00000522526.6	TSL:1	c.646G>A	p.Asp216Asn	missense	Exon 6 of 10	ENSP00000429278.2	Q8IZ02-3
	LRRC34	ENST00000895445.1		c.562G>A	p.Asp188Asn	missense	Exon 5 of 10	ENSP00000565504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000169 AC: 4 AN: 236306 AF XY: 0.0000235

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000232

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1435316 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 713158

African (AFR) AF: 0.00 AC: 0 AN: 32434

American (AMR) AF: 0.00 AC: 0 AN: 41470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25446

East Asian (EAS) AF: 0.0000773 AC: 3 AN: 38810

South Asian (SAS) AF: 0.00 AC: 0 AN: 81044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098652

Other (OTH) AF: 0.0000169 AC: 1 AN: 59078

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	Benign	0.24
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.92	T
PhyloP100		6.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Benign	0.12	T
Sift4G	Uncertain	0.021	D
Polyphen		0.75	P
Vest4		0.75
MVP		0.51
MPC		0.38
ClinPred		0.65	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.58
Mutation Taster		=69/31	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: rs746708653; hg19: chr3-169521852;