chr17-32021381-G-C

Position:

• chr17-32021381-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000341671.12(LRRC37B):​c.235G>C​(p.Ala79Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC37B ENST00000341671.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.263

Genes affected

LRRC37B (HGNC:29070): (leucine rich repeat containing 37B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10727948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37B	NM_001321350.2	c.1-12G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000543378.7
LRRC37B	NM_052888.3	c.235G>C	p.Ala79Pro	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37B	ENST00000543378.7	c.1-12G>C		splice_polypyrimidine_tract_variant, intron_variant		2	NM_001321350.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461618 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727090

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.235G>C (p.A79P) alteration is located in exon 1 (coding exon 1) of the LRRC37B gene. This alteration results from a G to C substitution at nucleotide position 235, causing the alanine (A) at amino acid position 79 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	.;T;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.75	T;T;T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.9	.;.;M;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.9	N;.;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D;.;D;D
Sift4G	Benign	0.31	T;T;T;T
Polyphen		1.0	.;.;D;D
Vest4		0.084
MutPred		0.13		.;.;Gain of glycosylation at A79 (P = 0.0073);Gain of glycosylation at A79 (P = 0.0073);
MVP		0.20
MPC		0.34
ClinPred		0.21	T
GERP RS		-2.5
Varity_R		0.27
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-30348400;