13-45550301-C-T

Variant names:

• chr13-45550301-C-T
• rs1444782514
• NM_182542.3:c.1423G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182542.3(ERICH6B):​c.1423G>A​(p.Gly475Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ERICH6B NM_182542.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

Genes affected

ERICH6B (HGNC:26523): (glutamate rich 6B)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERICH6B	NM_182542.3	c.1423G>A	p.Gly475Arg	missense_variant	Exon 12 of 15	ENST00000298738.3	NP_872348.2
ERICH6B	XM_011534965.3	c.1423G>A	p.Gly475Arg	missense_variant	Exon 11 of 14		XP_011533267.1
ERICH6B	XM_017020418.2	c.1423G>A	p.Gly475Arg	missense_variant	Exon 11 of 14		XP_016875907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERICH6B	ENST00000298738.3	c.1423G>A	p.Gly475Arg	missense_variant	Exon 12 of 15	2	NM_182542.3	ENSP00000298738.2
ERICH6B	ENST00000482992.1	n.54G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3
ERICH6B	ENST00000504261.5	n.-33G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000639 AC: 1 AN: 156490 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82950

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000286 AC: 4 AN: 1399192 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 690110

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1423G>A (p.G475R) alteration is located in exon 12 (coding exon 10) of the ERICH6B gene. This alteration results from a G to A substitution at nucleotide position 1423, causing the glycine (G) at amino acid position 475 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	0.084
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.43		Gain of MoRF binding (P = 0.0115);
MVP		0.16
ClinPred		0.88	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.32		Position offset: 15

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

Publications

LitVar

Other links and lift over

dbSNP: rs1444782514; hg19: chr13-46124436;