17-32021177-C-T

Variant names:

• chr17-32021177-C-T
• rs780110966
• ENST00000341671.12:c.31C>T

Variant summary

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

The NM_052888.3(LRRC37B):​c.31C>T​(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRRC37B NM_052888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

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=0.12455183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC37B	NM_001321350.2	c.1-216C>T		intron_variant	Intron 3 of 14	ENST00000543378.7	NP_001308279.1
LRRC37B	NM_052888.3	c.31C>T	p.Pro11Ser	missense_variant	Exon 1 of 12		NP_443120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC37B	ENST00000543378.7	c.1-216C>T		intron_variant	Intron 3 of 14	2	NM_001321350.2	ENSP00000443345.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461148 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726886

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.66
DANN	Benign	0.90
DEOGEN2	Benign	0.027	.;T;T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.77	T;T;T;.
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	.;.;M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D;.;D;D
REVEL	Benign	0.044
Sift	Benign	0.043	D;.;T;D
Sift4G	Uncertain	0.048	D;D;D;D
Polyphen		0.96	.;.;D;D
Vest4		0.073
MutPred		0.45		.;.;Gain of MoRF binding (P = 0.0333);Gain of MoRF binding (P = 0.0333);
MVP		0.36
MPC		0.085
ClinPred		0.13	T
GERP RS		-2.2
Varity_R		0.042
gMVP		0.17

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: rs780110966; hg19: chr17-30348196;