chr13-39344004-C-A

Position:

• chr13-39344004-C-A

Variant summary

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

The NM_005780.3(LHFPL6):​c.535G>T​(p.Ala179Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LHFPL6 NM_005780.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.313

Genes affected

LHFPL6 (HGNC:6586): (LHFPL tetraspan subfamily member 6) 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. This gene is fused to a high-mobility group gene in a translocation-associated lipoma. Mutations in another LHFP-like gene result in deafness in humans and mice. Alternatively spliced transcript variants have been found; however, their full-length nature is not known. [provided by RefSeq, Jul 2008]

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=0.11708814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHFPL6	NM_005780.3	c.535G>T	p.Ala179Ser	missense_variant	4/4	ENST00000379589.4	NP_005771.1
LHFPL6	XM_011534861.2	c.535G>T	p.Ala179Ser	missense_variant	4/4		XP_011533163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHFPL6	ENST00000379589.4	c.535G>T	p.Ala179Ser	missense_variant	4/4	1	NM_005780.3	ENSP00000368908	P1
LHFPL6	ENST00000648377.1	c.535G>T	p.Ala179Ser	missense_variant, NMD_transcript_variant	4/14			ENSP00000496801

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Dec 30, 2023

The c.535G>T (p.A179S) alteration is located in exon 4 (coding exon 3) of the LHFP gene. This alteration results from a G to T substitution at nucleotide position 535, causing the alanine (A) at amino acid position 179 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.043
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.023	D
Polyphen		0.078	B
Vest4		0.084
MutPred		0.58		Gain of glycosylation at A179 (P = 0.0141);
MVP		0.37
MPC		0.34
ClinPred		0.14	T
GERP RS		0.91
Varity_R		0.065
gMVP		0.32

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: chr13-39918141;