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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173849.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSC	NM_173849.3	MANE Select	c.400C>A	p.Gln134Lys	missense	Exon 2 of 3	NP_776248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSC	ENST00000238558.5	TSL:1 MANE Select	c.400C>A	p.Gln134Lys	missense	Exon 2 of 3	ENSP00000238558.3

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over