X-110346880-C-T

Variant names:

• chrX-110346880-C-T
• rs1242682271
• NM_001396022.1:c.30G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001396022.1(GNG5B):​c.30G>A​(p.Thr10Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000194 in 514,826 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T10T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: GNG5B NM_001396022.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 0 publications found

Genes affected

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• 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>A	p.Thr10Thr	synonymous	Exon 1 of 1	NP_001382951.1	A0A804HLA8
	AMMECR1	NM_001171689.2		c.-147-29031G>A		intron	N/A	NP_001165160.1	Q9Y4X0-4

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000194 AC: 1 AN: 514826 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 170222

African (AFR) AF: 0.00 AC: 0 AN: 15016

American (AMR) AF: 0.00 AC: 0 AN: 33053

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15641

East Asian (EAS) AF: 0.00 AC: 0 AN: 26978

South Asian (SAS) AF: 0.00 AC: 0 AN: 41493

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39469

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 313249

Other (OTH) AF: 0.0000373 AC: 1 AN: 26807

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.8
DANN	Uncertain	0.98
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1242682271; hg19: chrX-109590108; COSMIC: COSV64438538;