chr17-46297514-C-T

Variant names:

• chr17-46297514-C-T
• rs1480255894
• NM_014834.4:c.2381C>T

Variant summary

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

The NM_014834.4(LRRC37A):​c.2381C>T​(p.Pro794Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P794S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 8)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.103
• 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=0.094444335).

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.2381C>T	p.Pro794Leu	missense	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+2012G>A		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+2012G>A		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.2381C>T	p.Pro794Leu	missense	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2381C>T	p.Pro794Leu	missense	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2280C>T		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes AF: 0.000111 AC: 7 AN: 63232 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.000405

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

GnomAD2 exomes AF: 0.000133 AC: 4 AN: 30028 AF XY: 0.0000661

Gnomad AFR exome AF: 0.000251

Gnomad AMR exome AF: 0.000570

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: 0.0000200 AC: 12 AN: 600908 Hom.: 0 Cov.: 7 AF XY: 0.0000123 AC XY: 4 AN XY: 323990

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

African (AFR) AF: 0.000344 AC: 6 AN: 17428

American (AMR) AF: 0.000219 AC: 6 AN: 27366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19150

East Asian (EAS) AF: 0.00 AC: 0 AN: 19336

South Asian (SAS) AF: 0.00 AC: 0 AN: 62956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 378842

Other (OTH) AF: 0.00 AC: 0 AN: 30950

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00146302), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000111 AC: 7 AN: 63300 Hom.: 0 Cov.: 8 AF XY: 0.000136 AC XY: 4 AN XY: 29392

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

African (AFR) AF: 0.000404 AC: 7 AN: 17344

American (AMR) AF: 0.00 AC: 0 AN: 4520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1996

East Asian (EAS) AF: 0.00 AC: 0 AN: 174

South Asian (SAS) AF: 0.00 AC: 0 AN: 1224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 50

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 34748

Other (OTH) AF: 0.00 AC: 0 AN: 838

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000353194), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 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	0.10
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.8
DANN	Benign	0.85
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.10
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.069
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.013	D
Polyphen		0.20	B
Vest4		0.15
MutPred		0.29		Gain of stability (P = 0.0053)
MVP		0.068
ClinPred		0.15	T
GERP RS		1.0
Varity_R		0.062
gMVP		0.12

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: rs1480255894; hg19: chr17-44374880;