chr17-46297604-C-T

Variant names:

• chr17-46297604-C-T
• rs1170408266
• NM_014834.4:c.2471C>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.2471C>T​(p.Ala824Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 7)
  • 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: -0.627
• 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=0.071757495).

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.2471C>T	p.Ala824Val	missense	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+1922G>A		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+1922G>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.2471C>T	p.Ala824Val	missense	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2471C>T	p.Ala824Val	missense	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2190C>T		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes AF: 0.0000528 AC: 3 AN: 56846 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.00

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: 0.0000988

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000271 AC: 13 AN: 479566 Hom.: 0 Cov.: 4 AF XY: 0.0000156 AC XY: 4 AN XY: 257012

African (AFR) AF: 0.00 AC: 0 AN: 14632

American (AMR) AF: 0.00 AC: 0 AN: 23216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16508

East Asian (EAS) AF: 0.00 AC: 0 AN: 20258

South Asian (SAS) AF: 0.00 AC: 0 AN: 53340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2138

European-Non Finnish (NFE) AF: 0.0000453 AC: 13 AN: 287180

Other (OTH) AF: 0.00 AC: 0 AN: 27038

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000528 AC: 3 AN: 56846 Hom.: 0 Cov.: 7 AF XY: 0.0000385 AC XY: 1 AN XY: 25942

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

African (AFR) AF: 0.00 AC: 0 AN: 15588

American (AMR) AF: 0.00 AC: 0 AN: 4404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1798

East Asian (EAS) AF: 0.00 AC: 0 AN: 96

South Asian (SAS) AF: 0.00 AC: 0 AN: 1192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 150

European-Non Finnish (NFE) AF: 0.0000988 AC: 3 AN: 30356

Other (OTH) AF: 0.00 AC: 0 AN: 716

⚠️ 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: 0.0000843 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	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.8
DANN	Benign	0.79
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.63
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.055
Sift	Benign	0.19	T
Sift4G	Benign	0.84	T
Polyphen		0.039	B
Vest4		0.047
MutPred		0.23		Loss of disorder (P = 0.1231)
MVP		0.068
ClinPred		0.055	T
GERP RS		-4.0
Varity_R		0.044
gMVP		0.049

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: rs1170408266; hg19: chr17-44374970;