chr17-46512972-T-C

Variant names:

• chr17-46512972-T-C
• rs544698022
• NM_001006607.3:c.260T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001006607.3(LRRC37A2):​c.260T>C​(p.Leu87Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 15)
  • Exomes 𝑓: 0.000053 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.277
• Publications: 0 publications found

Genes affected

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17A (HGNC:24096): (ADP ribosylation factor like GTPase 17A) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037177652).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006607.3. 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
	LRRC37A2	NM_001006607.3	MANE Select	c.260T>C	p.Leu87Pro	missense	Exon 1 of 14	NP_001006608.2	A6NM11
	LRRC37A2	NM_001385803.1		c.260T>C	p.Leu87Pro	missense	Exon 1 of 14	NP_001372732.1
	ARL17A	NM_001288812.1		c.*22-4082A>G		intron	N/A	NP_001275741.1	Q8IVW1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A2	ENST00000576629.6	TSL:5 MANE Select	c.260T>C	p.Leu87Pro	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
	LRRC37A2	ENST00000706058.1		c.260T>C	p.Leu87Pro	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
	LRRC37A2	ENST00000705813.1		c.-89+1364T>C		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 38 AN: 84958 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000236

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

GnomAD2 exomes AF: 0.0000728 AC: 3 AN: 41204 AF XY: 0.0000996

Gnomad AFR exome AF: 0.000392

Gnomad AMR exome AF: 0.000135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000526 AC: 35 AN: 665872 Hom.: 0 Cov.: 4 AF XY: 0.0000425 AC XY: 14 AN XY: 329288

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00105 AC: 29 AN: 27700

American (AMR) AF: 0.000126 AC: 4 AN: 31798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9978

East Asian (EAS) AF: 0.00 AC: 0 AN: 34966

South Asian (SAS) AF: 0.00 AC: 0 AN: 35974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 461156

Other (OTH) AF: 0.0000684 AC: 2 AN: 29252

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000000144329), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000447 AC: 38 AN: 85052 Hom.: 0 Cov.: 15 AF XY: 0.000453 AC XY: 19 AN XY: 41948

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00109 AC: 36 AN: 33032

American (AMR) AF: 0.000236 AC: 2 AN: 8482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1312

East Asian (EAS) AF: 0.00 AC: 0 AN: 4154

South Asian (SAS) AF: 0.00 AC: 0 AN: 1992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 82

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 28138

Other (OTH) AF: 0.00 AC: 0 AN: 950

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000349618), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000253 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	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.70
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.28
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.088
Sift	Benign	0.13	T
Sift4G	Benign	0.22	T
Polyphen		0.33	B
Vest4		0.41
MutPred		0.13		Loss of stability (P = 0.0358)
MVP		0.085
ClinPred		0.025	T
GERP RS		1.1
Varity_R		0.19
gMVP		0.074

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs544698022; hg19: chr17-44590338;