11-118627814-C-G

Position:

• chr11-118627814-C-G

Variant summary

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

The NM_001144758.3(PHLDB1):​c.991C>G​(p.Leu331Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PHLDB1 NM_001144758.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

Genes affected

PHLDB1 (HGNC:23697): (pleckstrin homology like domain family B member 1) Involved in regulation of embryonic development; regulation of epithelial to mesenchymal transition; and regulation of microtubule cytoskeleton organization. Located in basal cortex. [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=0.14764005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDB1	NM_001144758.3	c.991C>G	p.Leu331Val	missense_variant	6/23	ENST00000600882.6	NP_001138230.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDB1	ENST00000600882.6	c.991C>G	p.Leu331Val	missense_variant	6/23	1	NM_001144758.3	ENSP00000469820

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452662 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723024

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

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

May 23, 2023

The c.991C>G (p.L331V) alteration is located in exon 7 (coding exon 5) of the PHLDB1 gene. This alteration results from a C to G substitution at nucleotide position 991, causing the leucine (L) at amino acid position 331 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T;T;.
Eigen	Benign	-0.058
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L
MutationTaster	Benign	0.83	N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.82	N;.;N
REVEL	Benign	0.040
Sift	Benign	0.034	D;.;D
Sift4G	Benign	0.26	T;T;T
Polyphen		0.36	B;B;B
Vest4		0.35
MutPred		0.18		Gain of methylation at R328 (P = 0.1137);Gain of methylation at R328 (P = 0.1137);Gain of methylation at R328 (P = 0.1137);
MVP		0.22
MPC		0.22
ClinPred		0.23	T
GERP RS		4.2
Varity_R		0.088
gMVP		0.19

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: chr11-118498530;