Genetic Variant GNG5B:p.Thr10Thr (chrX-110346880-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001396022.1(GNG5B):c.30G>T(p.Thr10Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

GNG5B
NM_001396022.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.07

Publications

0 publications found

Variant links:

Genes affected

GNG5B (HGNC:24826): (G protein subunit gamma 5B)

GNG5B links:

AMMECR1 (HGNC:467): (AMMECR nuclear protein 1) The exact function of this gene is not known, however, submicroscopic deletion of the X chromosome including this gene, COL4A5, and FACL4 genes, result in a contiguous gene deletion syndrome, the AMME complex (Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

AMMECR1 Gene-Disease associations (from GenCC):

midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Illumina
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

AMMECR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant X-110346880-C-A is Benign according to our data. Variant chrX-110346880-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661193.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.07 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396022.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNG5B	NM_001396022.1	MANE Select	c.30G>T	p.Thr10Thr	synonymous	Exon 1 of 1	NP_001382951.1	A0A804HLA8
	AMMECR1	NM_001171689.2		c.-147-29031G>T		intron	N/A	NP_001165160.1	Q9Y4X0-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNG5B	ENST00000697560.1	MANE Select	c.30G>T	p.Thr10Thr	synonymous	Exon 1 of 1	ENSP00000513336.1	A0A804HLA8
GNG5B	ENST00000372054.3	TSL:6	c.30G>T	p.Thr10Thr	synonymous	Exon 3 of 3	ENSP00000508275.1	A0A804HLA8
AMMECR1	ENST00000372057.1	TSL:2	c.-147-29031G>T		intron	N/A	ENSP00000361127.1	Q9Y4X0-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

514826

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

170222

African (AFR)

AF:

0.00

AC:

AN:

15016

American (AMR)

AF:

0.00

AC:

AN:

33053

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15641

East Asian (EAS)

AF:

0.00

AC:

AN:

26977

South Asian (SAS)

AF:

0.00

AC:

AN:

41493

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39469

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3120

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

313250

Other (OTH)

AF:

0.00

AC:

AN:

26807

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

5.2

(source)

DANN

Benign

0.97

PhyloP100

3.1

Mutation Taster

=95/5

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over