Variant chr6-25661630-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006998.4(SCGN):c.232A>T(p.Ile78Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SCGN
NM_006998.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.113

Variant links:

Genes affected

SCGN (HGNC:16941): (secretagogin, EF-hand calcium binding protein) The encoded protein is a secreted calcium-binding protein which is found in the cytoplasm. It is related to calbindin D-28K and calretinin. This protein is thought to be involved in KCL-stimulated calcium flux and cell proliferation. [provided by RefSeq, Jul 2008]

SCGN links:

ENSG00000290217 (HGNC:):

ENSG00000290217 links:

Genome browser will be placed here

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=0.22039911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCGN	NM_006998.4 linkuse as main transcript	c.232A>T	p.Ile78Phe	missense_variant	3/11	ENST00000377961.3	NP_008929.2	O76038

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCGN	ENST00000377961.3 linkuse as main transcript	c.232A>T	p.Ile78Phe	missense_variant	3/11	1	NM_006998.4	ENSP00000367197.2	O76038
ENSG00000290217	ENST00000703602.1 linkuse as main transcript	c.232A>T	p.Ile78Phe	missense_variant	3/12			ENSP00000515390.1	A0A994J4C2
SCGN	ENST00000612225.4 linkuse as main transcript	n.*11A>T		non_coding_transcript_exon_variant	2/10	5		ENSP00000484392.1	Q96P10
SCGN	ENST00000612225.4 linkuse as main transcript	n.*11A>T		3_prime_UTR_variant	2/10	5		ENSP00000484392.1	Q96P10

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

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

Apr 07, 2022

The c.232A>T (p.I78F) alteration is located in exon 3 (coding exon 3) of the SCGN gene. This alteration results from a A to T substitution at nucleotide position 232, causing the isoleucine (I) at amino acid position 78 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

0.098

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.1

DANN

Benign

0.77

DEOGEN2

Benign

0.17

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.58

M_CAP

Benign

0.0024

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.065

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.015

Vest4

0.29

MutPred

0.63

Loss of catalytic residue at L83 (P = 0.0416);

MVP

0.030

MPC

0.37

ClinPred

0.24

GERP RS

-6.4

Varity_R

0.20

gMVP

0.78

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