17-32021177-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12455183).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052888.3. 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
	LRRC37B	NM_001321350.2	MANE Select	c.1-216C>T		intron	N/A	NP_001308279.1	F5H5K1
	LRRC37B	NM_052888.3		c.31C>T	p.Pro11Ser	missense	Exon 1 of 12	NP_443120.2	Q96QE4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37B	ENST00000341671.12	TSL:1	c.31C>T	p.Pro11Ser	missense	Exon 1 of 12	ENSP00000340519.7	Q96QE4-1
	LRRC37B	ENST00000584368.5	TSL:1	c.31C>T	p.Pro11Ser	missense	Exon 1 of 10	ENSP00000463081.2	J3KTP0
	LRRC37B	ENST00000543378.7	TSL:2 MANE Select	c.1-216C>T		intron	N/A	ENSP00000443345.2	F5H5K1

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

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000192 AC: 1 AN: 5204

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111984

Other (OTH) AF: 0.0000166 AC: 1 AN: 60326

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-2.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.044
Sift	Benign	0.043	D
Sift4G	Uncertain	0.048	D
Polyphen		0.96	D
Vest4		0.073
MutPred		0.45		Gain of MoRF binding (P = 0.0333)
MVP		0.36
MPC		0.085
ClinPred		0.13	T
GERP RS		-2.2
PromoterAI		-0.035	Neutral
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

Other links and lift over

dbSNP: rs780110966; hg19: chr17-30348196;