Genetic Variant NM_173849.3:c.400C>A (chr14-94769173-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173849.3(GSC):c.400C>A(p.Gln134Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,411,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

GSC
NM_173849.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.94

Publications

0 publications found

Variant links:

Genes affected

GSC (HGNC:4612): (goosecoid homeobox) This gene encodes a member of the bicoid subfamily of the paired (PRD) homeobox family of proteins. The encoded protein acts as a transcription factor and may be autoregulatory. A similar protein in mice plays a role in craniofacial and rib cage development during embryogenesis. [provided by RefSeq, Jul 2008]

GSC Gene-Disease associations (from GenCC):

short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

GSC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40441534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSC	NM_173849.3 link	c.400C>A	p.Gln134Lys	missense_variant	Exon 2 of 3	ENST00000238558.5	NP_776248.1	P56915

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSC	ENST00000238558.5 link	c.400C>A	p.Gln134Lys	missense_variant	Exon 2 of 3	1	NM_173849.3	ENSP00000238558.3		P56915

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000598

AC:

AN:

167364

AF XY:

0.0000112

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1411140

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

697164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32346

American (AMR)

AF:

0.00

AC:

AN:

37456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25266

East Asian (EAS)

AF:

0.00

AC:

AN:

36886

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5070

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086582

Other (OTH)

AF:

0.00

AC:

AN:

58506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.021

MetaRNN

Benign

0.40

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

7.9

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.98

REVEL

Benign

0.18

Sift

Benign

0.033

Sift4G

Benign

0.68

Polyphen

0.92

Vest4

0.50

MutPred

0.34

Gain of ubiquitination at Q134 (P = 0.0138);

MVP

0.71

MPC

1.4

ClinPred

0.76

GERP RS

4.9

Varity_R

0.51

gMVP

0.65

Mutation Taster

=64/36

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over