17-46297344-A-T

Variant names:

• chr17-46297344-A-T
• NM_014834.4:c.2211A>T
• LRRC37A p.Pro737Pro

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_014834.4(LRRC37A):​c.2211A>T​(p.Pro737Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P737P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.

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.2211A>T	p.Pro737Pro	synonymous	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+2182T>A		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+2182T>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.2211A>T	p.Pro737Pro	synonymous	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2211A>T	p.Pro737Pro	synonymous	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2450A>T		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.47e-7 AC: 1 AN: 1181042 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 596236

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

African (AFR) AF: 0.00 AC: 0 AN: 29626

American (AMR) AF: 0.00 AC: 0 AN: 33358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24124

East Asian (EAS) AF: 0.00 AC: 0 AN: 20752

South Asian (SAS) AF: 0.00 AC: 0 AN: 77404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3682

European-Non Finnish (NFE) AF: 0.00000112 AC: 1 AN: 896852

Other (OTH) AF: 0.00 AC: 0 AN: 50068

⚠️ 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 Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-44374710;