19-44813458-A-G

Position:

• chr19-44813458-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005581.5(BCAM):​c.622A>G​(p.Thr208Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T208T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCAM NM_005581.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85

Genes affected

BCAM (HGNC:6722): (basal cell adhesion molecule (Lutheran blood group)) This gene encodes Lutheran blood group glycoprotein, a member of the immunoglobulin superfamily and a receptor for the extracellular matrix protein, laminin. The protein contains five extracellular immunoglobulin domains, a single transmembrane domain, and a short C-terminal cytoplasmic tail. This protein may play a role in epithelial cell cancer and in vaso-occlusion of red blood cells in sickle cell disease. Polymorphisms in this gene define some of the antigens in the Lutheran system and also the Auberger system. Inactivating variants of this gene result in the recessive Lutheran null phenotype, Lu(a-b-), of the Lutheran blood group. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11749509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAM	NM_005581.5	c.622A>G	p.Thr208Ala	missense_variant	6/15	ENST00000270233.12
BCAM	NM_001013257.2	c.622A>G	p.Thr208Ala	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAM	ENST00000270233.12	c.622A>G	p.Thr208Ala	missense_variant	6/15	1	NM_005581.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.622A>G (p.T208A) alteration is located in exon 6 (coding exon 6) of the BCAM gene. This alteration results from a A to G substitution at nucleotide position 622, causing the threonine (T) at amino acid position 208 to be replaced by an alanine (A). 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	0.10
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.25	T;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	0.96	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;.;.
REVEL	Benign	0.12
Sift	Benign	0.056	T;.;.
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.18	B;.;.
Vest4		0.33
MutPred		0.56		Loss of phosphorylation at T208 (P = 0.0231);Loss of phosphorylation at T208 (P = 0.0231);.;
MVP		0.31
MPC		0.25
ClinPred		0.24	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.44

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: chr19-45316715;