Variant 6-25681993-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006998.4(SCGN):c.514A>G(p.Asn172Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SCGN
NM_006998.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.97

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCGN	NM_006998.4 linkuse as main transcript	c.514A>G	p.Asn172Asp	missense_variant	7/11	ENST00000377961.3	NP_008929.2	O76038
LOC124901284	XR_007059517.1 linkuse as main transcript	n.2154T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SCGN	ENST00000377961.3 linkuse as main transcript	c.514A>G	p.Asn172Asp	missense_variant	7/11	1	NM_006998.4	ENSP00000367197.2	O76038
ENSG00000290217	ENST00000703602.1 linkuse as main transcript	c.514A>G	p.Asn172Asp	missense_variant	7/12			ENSP00000515390.1	A0A994J4C2
SCGN	ENST00000612225.4 linkuse as main transcript	n.*293A>G		non_coding_transcript_exon_variant	6/10	5		ENSP00000484392.1	Q96P10
SCGN	ENST00000612225.4 linkuse as main transcript	n.*293A>G		3_prime_UTR_variant	6/10	5		ENSP00000484392.1	Q96P10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251336

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Dec 20, 2023

The c.514A>G (p.N172D) alteration is located in exon 7 (coding exon 7) of the SCGN gene. This alteration results from a A to G substitution at nucleotide position 514, causing the asparagine (N) at amino acid position 172 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

0.19

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.68

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.0

REVEL

Benign

0.21

Sift

Benign

0.093

Sift4G

Benign

0.20

Polyphen

0.95

Vest4

0.53

MutPred

0.42

Gain of loop (P = 0.1069);

MVP

0.67

MPC

0.72

ClinPred

0.97

GERP RS

5.1

Varity_R

0.40

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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