3-120335948-T-C

Variant names:

• chr3-120335948-T-C
• rs140152656
• NM_001099678.2:c.506A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001099678.2(LRRC58):​c.506A>G​(p.Glu169Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00446 in 1,574,298 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E169Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0046 (25 hom.)
• Consequence: LRRC58 NM_001099678.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.10
• Publications: 5 publications found

Genes affected

LRRC58 (HGNC:26968): (leucine rich repeat containing 58)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05185336).
• BP6: Variant 3-120335948-T-C is Benign according to our data. Variant chr3-120335948-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2654060.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 25 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099678.2. 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
	LRRC58	NM_001099678.2	MANE Select	c.506A>G	p.Glu169Gly	missense	Exon 2 of 4	NP_001093148.1	Q96CX6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC58	ENST00000295628.4	TSL:1 MANE Select	c.506A>G	p.Glu169Gly	missense	Exon 2 of 4	ENSP00000295628.3	Q96CX6
	LRRC58	ENST00000946153.1		c.506A>G	p.Glu169Gly	missense	Exon 2 of 4	ENSP00000616212.1
	LRRC58	ENST00000886041.1		c.501-809A>G		intron	N/A	ENSP00000556100.1

Frequencies

GnomAD3 genomes AF: 0.00315 AC: 479 AN: 152032 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00305 AC: 733 AN: 240514 AF XY: 0.00289

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.000411

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00288

Gnomad NFE exome AF: 0.00534

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00460 AC: 6548 AN: 1422148 Hom.: 25 Cov.: 27 AF XY: 0.00437 AC XY: 3101 AN XY: 708996

African (AFR) AF: 0.000713 AC: 23 AN: 32248

American (AMR) AF: 0.00131 AC: 56 AN: 42808

Ashkenazi Jewish (ASJ) AF: 0.000273 AC: 7 AN: 25612

East Asian (EAS) AF: 0.00 AC: 0 AN: 39394

South Asian (SAS) AF: 0.0000477 AC: 4 AN: 83892

European-Finnish (FIN) AF: 0.00237 AC: 124 AN: 52300

Middle Eastern (MID) AF: 0.000201 AC: 1 AN: 4986

European-Non Finnish (NFE) AF: 0.00565 AC: 6117 AN: 1081904

Other (OTH) AF: 0.00366 AC: 216 AN: 59004

GnomAD4 genome AF: 0.00315 AC: 479 AN: 152150 Hom.: 1 Cov.: 33 AF XY: 0.00286 AC XY: 213 AN XY: 74402

African (AFR) AF: 0.00128 AC: 53 AN: 41510

American (AMR) AF: 0.00111 AC: 17 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00208 AC: 22 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00560 AC: 381 AN: 68008

Other (OTH) AF: 0.00190 AC: 4 AN: 2102

Alfa AF: 0.00431 Hom.: 3

Bravo AF: 0.00324

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00363 AC: 14

ESP6500AA AF: 0.00168 AC: 6

ESP6500EA AF: 0.00627 AC: 51

ExAC AF: 0.00312 AC: 377

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.083	T
Polyphen		0.95	P
Vest4		0.84
MVP		0.85
MPC		2.1
ClinPred		0.032	T
GERP RS		5.3
Varity_R		0.48
gMVP		0.70
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs140152656; hg19: chr3-120054795; COSMIC: COSV99820342;