17-46297478-C-G

Position:

• chr17-46297478-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014834.4(LRRC37A):​c.2345C>G​(p.Thr782Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000089 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00012 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044703484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37A	NM_014834.4	c.2345C>G	p.Thr782Ser	missense_variant	1/14	ENST00000320254.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37A	ENST00000320254.5	c.2345C>G	p.Thr782Ser	missense_variant	1/14	1	NM_014834.4	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 112118 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.0000303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00244

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000185

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000118 AC: 137 AN: 1162152 Hom.: 6 Cov.: 23 AF XY: 0.000153 AC XY: 90 AN XY: 588788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000278

Gnomad4 ASJ exome AF: 0.0000415

Gnomad4 EAS exome AF: 0.000231

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000403

Gnomad4 OTH exome AF: 0.000161

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000891 AC: 10 AN: 112202 Hom.: 0 Cov.: 17 AF XY: 0.000132 AC XY: 7 AN XY: 53000

Gnomad4 AFR AF: 0.0000302

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00244

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000185

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.9
DANN	Benign	0.73
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.11
Sift	Benign	0.17	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.88	.;P
Vest4		0.035
MutPred		0.25		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.068
ClinPred		0.32	T
GERP RS		-4.0
Varity_R		0.036
gMVP		0.046

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

Publications

LitVar

Other links and lift over

dbSNP: rs879108776; hg19: chr17-44374844;