NM_014834.4:c.2125C>G

Variant names:

• chr17-46297258-C-G
• rs1218255775
• NM_014834.4:c.2125C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014834.4(LRRC37A):​c.2125C>G​(p.Gln709Glu) 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 0.00010 (0 hom., cov: 5)
  • Exomes 𝑓: 0.000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

Genes affected

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09511909).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014834.4. 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
	LRRC37A	NM_014834.4	MANE Select	c.2125C>G	p.Gln709Glu	missense	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+2268G>C		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+2268G>C		intron	N/A	NP_001339698.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A	ENST00000320254.5	TSL:1 MANE Select	c.2125C>G	p.Gln709Glu	missense	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2125C>G	p.Gln709Glu	missense	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2536C>G		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 4 AN: 39776 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.000409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000266 AC: 11 AN: 413958 Hom.: 0 Cov.: 0 AF XY: 0.0000269 AC XY: 6 AN XY: 223068

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

African (AFR) AF: 0.000854 AC: 10 AN: 11706

American (AMR) AF: 0.0000670 AC: 1 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12658

East Asian (EAS) AF: 0.00 AC: 0 AN: 14202

South Asian (SAS) AF: 0.00 AC: 0 AN: 43200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1862

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 256488

Other (OTH) AF: 0.00 AC: 0 AN: 23700

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000103062), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000100 AC: 4 AN: 39848 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 18542

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

African (AFR) AF: 0.000407 AC: 4 AN: 9834

American (AMR) AF: 0.00 AC: 0 AN: 2762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1358

East Asian (EAS) AF: 0.00 AC: 0 AN: 80

South Asian (SAS) AF: 0.00 AC: 0 AN: 596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 23320

Other (OTH) AF: 0.00 AC: 0 AN: 514

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00180467), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 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	0.092
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.092
Sift	Benign	0.12	T
Sift4G	Benign	0.14	T
Polyphen		0.46	P
Vest4		0.24
MutPred		0.13		Gain of catalytic residue at Q709 (P = 0.1352)
MVP		0.043
ClinPred		0.21	T
GERP RS		1.7
Varity_R		0.11
gMVP		0.031

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: rs1218255775; hg19: chr17-44374624;