rs1175569023

Variant names:

• chr17-46514964-T-C
• rs1175569023
• NM_001006607.3:c.2252T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-46514964-T-C
• chr17-46514964-T-G

Variant summary

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

The NM_001006607.3(LRRC37A2):​c.2252T>C​(p.Leu751Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. L751R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• 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=0.045775145).

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.2252T>C	p.Leu751Pro	missense	Exon 1 of 14	NP_001006608.2	A6NM11
	LRRC37A2	NM_001385803.1		c.2252T>C	p.Leu751Pro	missense	Exon 1 of 14	NP_001372732.1
	ARL17A	NM_001288812.1		c.*21+2130A>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.2252T>C	p.Leu751Pro	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
	LRRC37A2	ENST00000706058.1		c.2252T>C	p.Leu751Pro	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
	LRRC37A2	ENST00000705813.1		c.-88-2398T>C		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD2 exomes AF: 0.00000758 AC: 1 AN: 132008 AF XY: 0.0000145

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000665

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: 0.00000144 AC: 1 AN: 695672 Hom.: 0 Cov.: 4 AF XY: 0.00000292 AC XY: 1 AN XY: 342958

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

African (AFR) AF: 0.00 AC: 0 AN: 22122

American (AMR) AF: 0.00 AC: 0 AN: 30904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10076

East Asian (EAS) AF: 0.0000298 AC: 1 AN: 33558

South Asian (SAS) AF: 0.00 AC: 0 AN: 36764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1522

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 497872

Other (OTH) AF: 0.00 AC: 0 AN: 29356

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	2.3
DANN	Benign	0.39
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00064	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.67	N
PhyloP100		-0.14
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.17
Sift	Benign	0.23	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.33
MutPred		0.25		Gain of glycosylation at L751 (P = 0.0359)
MVP		0.048
ClinPred		0.015	T
GERP RS		-0.97
Varity_R		0.040
gMVP		0.080

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: rs1175569023; hg19: chr17-44592330;