Variant 8-52565078-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000358543.9(ALKAL1):c.179C>T(p.Ser60Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000799 in 1,251,170 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 33)

Exomes 𝑓: 0.0000080 ( 1 hom. )

Consequence

ALKAL1
ENST00000358543.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.383

Variant links:

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]

ALKAL1 links:

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ACMG classification

Classification made for transcript

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=0.08404252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKAL1	NM_207413.4 linkuse as main transcript	c.179C>T	p.Ser60Phe	missense_variant	1/5	ENST00000358543.9	NP_997296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALKAL1	ENST00000358543.9 linkuse as main transcript	c.179C>T	p.Ser60Phe	missense_variant	1/5	1	NM_207413.4	ENSP00000351345.4		Q6UXT8-1
ALKAL1	ENST00000523939.1 linkuse as main transcript	c.179C>T	p.Ser60Phe	missense_variant	1/4	1		ENSP00000430953.1		Q6UXT8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000267

AC:

AN:

37514

Hom.:

AF XY:

0.0000491

AC XY:

AN XY:

20366

show subpopulations

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 SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000799

AC:

AN:

1251170

Hom.:

Cov.:

AF XY:

0.00000821

AC XY:

AN XY:

609116

show subpopulations

Gnomad4 AFR exome

AF:

0.0000811

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000678

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000298

Gnomad4 OTH exome

AF:

0.0000196

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.179C>T (p.S60F) alteration is located in exon 1 (coding exon 1) of the FAM150A gene. This alteration results from a C to T substitution at nucleotide position 179, causing the serine (S) at amino acid position 60 to be replaced by a phenylalanine (F). 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

0.077

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.043

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.96

D;.

Vest4

0.088

MutPred

0.13

Loss of phosphorylation at S60 (P = 0.0119);Loss of phosphorylation at S60 (P = 0.0119);

MVP

0.13

MPC

0.37

ClinPred

0.064

GERP RS

0.97

Varity_R

0.16

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over