11-118627444-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001144758.3(PHLDB1):c.621G>C(p.Glu207Asp) 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. 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)
• Consequence: PHLDB1 NM_001144758.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.602

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06788838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHLDB1	NM_001144758.3	c.621G>C	p.Glu207Asp	missense_variant	6/23	ENST00000600882.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLDB1	ENST00000600882.6	c.621G>C	p.Glu207Asp	missense_variant	6/23	1	NM_001144758.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Feb 17, 2024

The c.621G>C (p.E207D) alteration is located in exon 7 (coding exon 5) of the PHLDB1 gene. This alteration results from a G to C substitution at nucleotide position 621, causing the glutamic acid (E) at amino acid position 207 to be replaced by an aspartic acid (D). 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	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.016	T;.;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;.;L;L
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.72	N;.;.;N
REVEL	Benign	0.091
Sift	Benign	0.28	T;.;.;T
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.0060	B;.;B;B
Vest4		0.18
MutPred		0.075		Loss of glycosylation at P209 (P = 0.1944);Loss of glycosylation at P209 (P = 0.1944);Loss of glycosylation at P209 (P = 0.1944);Loss of glycosylation at P209 (P = 0.1944);
MVP		0.17
MPC		0.20
ClinPred		0.18	T
GERP RS		4.8
Varity_R		0.12
gMVP		0.21

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: chr11-118498160;