11-62663244-G-C

Variant names:

• chr11-62663244-G-C
• NM_024099.5:c.753C>G

Variant summary

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

The NM_024099.5(LBHD1):​c.753C>G​(p.Ser251Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LBHD1 NM_024099.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74

Genes affected

LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

C11orf98 (HGNC:51238): (chromosome 11 open reading frame 98) This gene shares three exons in common with another gene, LBH domain containing 1 (GeneID:79081), but the encoded protein uses a reading frame that is different from that of the LBH domain containing 1 gene. [provided by RefSeq, Nov 2017]

ENSG00000255432 (HGNC:):

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=0.14468297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBHD1	NM_024099.5	c.753C>G	p.Ser251Arg	missense_variant	Exon 6 of 7	ENST00000354588.8	NP_077004.2
C11orf98	NM_001286086.2	c.254C>G	p.Ala85Gly	missense_variant	Exon 3 of 4	ENST00000524958.6	NP_001273015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBHD1	ENST00000354588.8	c.753C>G	p.Ser251Arg	missense_variant	Exon 6 of 7	1	NM_024099.5	ENSP00000346600.3
C11orf98	ENST00000524958.6	c.254C>G	p.Ala85Gly	missense_variant	Exon 3 of 4	2	NM_001286086.2	ENSP00000432523.2
ENSG00000255432	ENST00000528405.1	c.254C>G	p.Ala85Gly	missense_variant	Exon 3 of 4	4		ENSP00000435188.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.753C>G (p.S251R) alteration is located in exon 6 (coding exon 5) of the LBHD1 gene. This alteration results from a C to G substitution at nucleotide position 753, causing the serine (S) at amino acid position 251 to be replaced by an arginine (R). 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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	.;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.32	T;T;T
Vest4		0.29
MutPred		0.16		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP		0.44
MPC		0.38
ClinPred		0.84	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.048

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62430716;