NM_001006607.3:c.710C>T

Variant names:

• chr17-46513422-C-T
• rs1195171075
• NM_001006607.3:c.710C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001006607.3(LRRC37A2):​c.710C>T​(p.Ser237Leu) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0069 (182 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.731
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023373663).
• BP6: Variant 17-46513422-C-T is Benign according to our data. Variant chr17-46513422-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2408162.Status of the report is criteria_provided_single_submitter, 1 stars.

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.710C>T	p.Ser237Leu	missense	Exon 1 of 14	NP_001006608.2	A6NM11
	LRRC37A2	NM_001385803.1		c.710C>T	p.Ser237Leu	missense	Exon 1 of 14	NP_001372732.1
	ARL17A	NM_001288812.1		c.*21+3672G>A		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.710C>T	p.Ser237Leu	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
	LRRC37A2	ENST00000706058.1		c.710C>T	p.Ser237Leu	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
	LRRC37A2	ENST00000705813.1		c.-89+1814C>T		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes AF: 0.0311 AC: 547 AN: 17604 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

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: 0.0337

GnomAD2 exomes AF: 0.0120 AC: 28 AN: 2326 AF XY: 0.0119

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00301

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00688 AC: 1546 AN: 224754 Hom.: 182 Cov.: 0 AF XY: 0.00616 AC XY: 716 AN XY: 116268

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

African (AFR) AF: 0.105 AC: 1128 AN: 10758

American (AMR) AF: 0.00815 AC: 101 AN: 12388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5174

East Asian (EAS) AF: 0.00 AC: 0 AN: 27482

South Asian (SAS) AF: 0.00125 AC: 24 AN: 19254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18804

Middle Eastern (MID) AF: 0.00983 AC: 7 AN: 712

European-Non Finnish (NFE) AF: 0.000437 AC: 51 AN: 116752

Other (OTH) AF: 0.0175 AC: 235 AN: 13430

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0311 AC: 550 AN: 17686 Hom.: 0 Cov.: 0 AF XY: 0.0302 AC XY: 254 AN XY: 8408

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

African (AFR) AF: 0.0828 AC: 526 AN: 6354

American (AMR) AF: 0.00999 AC: 18 AN: 1802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 260

East Asian (EAS) AF: 0.00 AC: 0 AN: 1486

South Asian (SAS) AF: 0.00 AC: 0 AN: 304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 26

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 5376

Other (OTH) AF: 0.0333 AC: 6 AN: 180

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0230 Hom.: 4

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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	0.082
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.2
DANN	Benign	0.40
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.73
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.014
Sift	Benign	0.57	T
Sift4G	Benign	0.27	T
Polyphen		0.0030	B
Vest4		0.17
MutPred		0.16		Loss of phosphorylation at S237 (P = 0.0327)
ClinPred		0.0090	T
GERP RS		0.095
Varity_R		0.044
gMVP		0.047
Mutation Taster		=99/1	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: rs1195171075; hg19: chr17-44590788; COSMIC: COSV61004394; COSMIC: COSV61004394;