X-112671360-G-C

Variant names:

• chrX-112671360-G-C
• rs138438376
• NM_178175.4:c.31C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178175.4(LHFPL1):​c.31C>G​(p.Leu11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,210,323 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. L11F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: LHFPL1 NM_178175.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

Genes affected

LHFPL1 (HGNC:6587): (LHFPL tetraspan subfamily member 1) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in one LHFP-like gene result in deafness in humans and mice, and a second LHFP-like gene is fused to a high-mobility group gene in a translocation-associated lipoma. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000303644 (HGNC:):

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=0.21873853).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178175.4. 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
	LHFPL1	NM_178175.4	MANE Select	c.31C>G	p.Leu11Val	missense	Exon 2 of 4	NP_835469.1	Q86WI0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL1	ENST00000371968.8	TSL:1 MANE Select	c.31C>G	p.Leu11Val	missense	Exon 2 of 4	ENSP00000361036.3	Q86WI0-1
	LHFPL1	ENST00000864007.1		c.31C>G	p.Leu11Val	missense	Exon 2 of 4	ENSP00000534066.1
	LHFPL1	ENST00000864010.1		c.31C>G	p.Leu11Val	missense	Exon 2 of 4	ENSP00000534070.1

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112164 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183384 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098159 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363519

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842070

Other (OTH) AF: 0.00 AC: 0 AN: 46095

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112164 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34314

African (AFR) AF: 0.00 AC: 0 AN: 30837

American (AMR) AF: 0.00 AC: 0 AN: 10614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3580

South Asian (SAS) AF: 0.00 AC: 0 AN: 2675

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6145

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53231

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.0000540 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.12
Sift	Benign	0.34	T
Sift4G	Benign	0.94	T
Polyphen		0.019	B
Vest4		0.23
MutPred		0.41		Gain of MoRF binding (P = 0.0725)
MVP		0.50
MPC		0.11
ClinPred		0.050	T
GERP RS		4.6
Varity_R		0.13
gMVP		0.79
Mutation Taster		=93/7	polymorphism

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: rs138438376; hg19: chrX-111914588;