17-46297705-C-T

Variant names:

• chr17-46297705-C-T
• rs1441152025
• NM_014834.4:c.2572C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_014834.4(LRRC37A):​c.2572C>T​(p.Pro858Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (1 hom., cov: 5)
  • Exomes 𝑓: 0.0014 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0810
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13850701).
• BP6: Variant 17-46297705-C-T is Benign according to our data. Variant chr17-46297705-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2410289.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2572C>T	p.Pro858Ser	missense	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+1821G>A		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+1821G>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.2572C>T	p.Pro858Ser	missense	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2572C>T	p.Pro858Ser	missense	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2089C>T		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes AF: 0.00882 AC: 274 AN: 31058 Hom.: 1 Cov.: 5

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00204

Gnomad ASJ AF: 0.00198

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00943

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00142 AC: 562 AN: 394438 Hom.: 4 Cov.: 0 AF XY: 0.00120 AC XY: 250 AN XY: 207832

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

African (AFR) AF: 0.0369 AC: 431 AN: 11694

American (AMR) AF: 0.00211 AC: 33 AN: 15656

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 18 AN: 12984

East Asian (EAS) AF: 0.00 AC: 0 AN: 15102

South Asian (SAS) AF: 0.0000935 AC: 4 AN: 42768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1868

European-Non Finnish (NFE) AF: 0.0000567 AC: 14 AN: 247052

Other (OTH) AF: 0.00263 AC: 62 AN: 23604

⚠️ 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: 0.00877 AC: 273 AN: 31116 Hom.: 1 Cov.: 5 AF XY: 0.00822 AC XY: 112 AN XY: 13620

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

African (AFR) AF: 0.0292 AC: 262 AN: 8984

American (AMR) AF: 0.00204 AC: 5 AN: 2452

Ashkenazi Jewish (ASJ) AF: 0.00198 AC: 2 AN: 1010

East Asian (EAS) AF: 0.00 AC: 0 AN: 72

South Asian (SAS) AF: 0.00 AC: 0 AN: 792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 15636

Other (OTH) AF: 0.00939 AC: 4 AN: 426

⚠️ 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: 0.00624 Hom.: 0

ClinVar

ClinVar submissions

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.081
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.062
Sift	Benign	0.30	T
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.091
MutPred		0.27		Gain of glycosylation at P858 (P = 0.0424)
MVP		0.093
ClinPred		0.49	T
GERP RS		1.3
Varity_R		0.14
gMVP		0.067
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1441152025; hg19: chr17-44375071;