13-102807322-A-G

Variant names:

• chr13-102807322-A-G
• NM_017693.4:c.55A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017693.4(BIVM):​c.55A>G​(p.Lys19Glu) variant causes a missense 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BIVM NM_017693.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65

Genes affected

BIVM (HGNC:16034): (basic, immunoglobulin-like variable motif containing) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BIVM-ERCC5 (HGNC:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061400175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM	NM_017693.4	c.55A>G	p.Lys19Glu	missense_variant	Exon 3 of 11	ENST00000257336.6	NP_060163.2
BIVM-ERCC5	NM_001204425.2	c.55A>G	p.Lys19Glu	missense_variant	Exon 1 of 23		NP_001191354.2
BIVM	NM_001159596.2	c.-210+7801A>G		intron_variant	Intron 1 of 8		NP_001153068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIVM	ENST00000257336.6	c.55A>G	p.Lys19Glu	missense_variant	Exon 3 of 11	1	NM_017693.4	ENSP00000257336.1
BIVM-ERCC5	ENST00000639435.1	c.55A>G	p.Lys19Glu	missense_variant	Exon 3 of 25	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132	c.-633A>G		5_prime_UTR_variant	Exon 2 of 24	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.55A>G (p.K19E) alteration is located in exon 3 (coding exon 1) of the BIVM gene. This alteration results from a A to G substitution at nucleotide position 55, causing the lysine (K) at amino acid position 19 to be replaced by a glutamic acid (E). 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	0.074
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	T;T;.
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.061	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.;.
PROVEAN	Benign	-0.48	N;.;.
REVEL	Benign	0.060
Sift	Benign	0.26	T;.;.
Sift4G	Benign	0.89	T;.;.
Polyphen		0.013	B;.;.
Vest4		0.19
MutPred		0.20		Loss of ubiquitination at K19 (P = 0.0023);Loss of ubiquitination at K19 (P = 0.0023);Loss of ubiquitination at K19 (P = 0.0023);
MVP		0.040
MPC		0.38
ClinPred		0.093	T
GERP RS		1.7
Varity_R		0.065
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr13-103459672;