14-94769021-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_173849.3(GSC):c.552C>T(p.Tyr184=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00114 in 1,597,246 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (34 hom.)
• Consequence: GSC NM_173849.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.79

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 14-94769021-G-A is Benign according to our data. Variant chr14-94769021-G-A is described in ClinVar as [Benign]. Clinvar id is 708174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0018 (274/152350) while in subpopulation EAS AF= 0.0458 (237/5170). AF 95% confidence interval is 0.0411. There are 5 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSC	NM_173849.3	c.552C>T	p.Tyr184=	synonymous_variant	2/3	ENST00000238558.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSC	ENST00000238558.5	c.552C>T	p.Tyr184=	synonymous_variant	2/3	1	NM_173849.3	P1

Frequencies

GnomAD3 genomes AF: 0.00180 AC: 274 AN: 152232 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00339 AC: 733 AN: 215996 Hom.: 14 AF XY: 0.00295 AC XY: 346 AN XY: 117244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000633

Gnomad ASJ exome AF: 0.00521

Gnomad EAS exome AF: 0.0399

Gnomad SAS exome AF: 0.000592

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000633

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00107 AC: 1549 AN: 1444896 Hom.: 34 Cov.: 33 AF XY: 0.00103 AC XY: 738 AN XY: 717056

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.0000940

Gnomad4 ASJ exome AF: 0.00444

Gnomad4 EAS exome AF: 0.0296

Gnomad4 SAS exome AF: 0.000625

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000272

Gnomad4 OTH exome AF: 0.00323

GnomAD4 genome AF: 0.00180 AC: 274 AN: 152350 Hom.: 5 Cov.: 33 AF XY: 0.00197 AC XY: 147 AN XY: 74496

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.0458

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000932 Hom.: 0

Bravo AF: 0.00228

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	12
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs117555620; hg19: chr14-95235358; COSMIC: COSV53076934; COSMIC: COSV53076934;