13-45549948-C-A

Variant names:

• chr13-45549948-C-A
• NM_182542.3:c.1591G>T

Variant summary

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

The NM_182542.3(ERICH6B):​c.1591G>T​(p.Ala531Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERICH6B NM_182542.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.37

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.1591G>T	p.Ala531Ser	missense_variant	Exon 13 of 15	ENST00000298738.3	NP_872348.2
ERICH6B	XM_011534965.3	c.1663G>T	p.Ala555Ser	missense_variant	Exon 12 of 14		XP_011533267.1
ERICH6B	XM_017020418.2	c.1591G>T	p.Ala531Ser	missense_variant	Exon 12 of 14		XP_016875907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERICH6B	ENST00000298738.3	c.1591G>T	p.Ala531Ser	missense_variant	Exon 13 of 15	2	NM_182542.3	ENSP00000298738.2
ERICH6B	ENST00000482992.1	n.294G>T		non_coding_transcript_exon_variant	Exon 3 of 4	3
ERICH6B	ENST00000504261.5	n.208G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1591G>T (p.A531S) alteration is located in exon 13 (coding exon 11) of the ERICH6B gene. This alteration results from a G to T substitution at nucleotide position 1591, causing the alanine (A) at amino acid position 531 to be replaced by a serine (S). 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	Benign	0.33
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.24
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.64		Gain of catalytic residue at L532 (P = 0.0013);
MVP		0.21
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-46124083;