chr8-52539893-G-T

Position:

• chr8-52539893-G-T

Variant summary

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

The ENST00000358543.9(ALKAL1):​c.263C>A​(p.Pro88Gln) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALKAL1 ENST00000358543.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.34

Genes affected

ALKAL1 (HGNC:33775): (ALK and LTK ligand 1) Enables receptor signaling protein tyrosine kinase activator activity and receptor tyrosine kinase binding activity. Involved in positive regulation of ERK1 and ERK2 cascade; positive regulation of ERK5 cascade; and positive regulation of neuron projection development. Predicted to be located in extracellular region. [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=0.2629131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKAL1	NM_207413.4	c.263C>A	p.Pro88Gln	missense_variant	3/5	ENST00000358543.9	NP_997296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALKAL1	ENST00000358543.9	c.263C>A	p.Pro88Gln	missense_variant	3/5	1	NM_207413.4	ENSP00000351345.4
ALKAL1	ENST00000523939.1	c.263C>A	p.Pro88Gln	missense_variant	3/4	1		ENSP00000430953.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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 10, 2023

The c.263C>A (p.P88Q) alteration is located in exon 3 (coding exon 3) of the FAM150A gene. This alteration results from a C to A substitution at nucleotide position 263, causing the proline (P) at amino acid position 88 to be replaced by a glutamine (Q). 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	0.15
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.081
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.26	B;.
Vest4		0.42
MutPred		0.18		Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);
MVP		0.12
MPC		0.68
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.38
gMVP		0.16

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: chr8-53452453;