6-42829054-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001393499.1(BICRAL):c.721A>G(p.Ser241Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: BICRAL NM_001393499.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69

Genes affected

BICRAL (HGNC:21111): (BICRA like chromatin remodeling complex associated protein) Predicted to be involved in positive regulation of transcription, DNA-templated. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, BICRAL
• BP4: Computational evidence support a benign effect (MetaRNN=0.082393914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICRAL	NM_001393499.1	c.721A>G	p.Ser241Gly	missense_variant	6/13	ENST00000314073.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICRAL	ENST00000314073.10	c.721A>G	p.Ser241Gly	missense_variant	6/13	1	NM_001393499.1	P1
BICRAL	ENST00000394168.1	c.721A>G	p.Ser241Gly	missense_variant	5/12	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.721A>G (p.S241G) alteration is located in exon 5 (coding exon 4) of the GLTSCR1L gene. This alteration results from a A to G substitution at nucleotide position 721, causing the serine (S) at amino acid position 241 to be replaced by a glycine (G). 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	0.066
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.0025
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.71	T;.;.
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.13
MutPred		0.18		Loss of glycosylation at S241 (P = 0.0231);Loss of glycosylation at S241 (P = 0.0231);Loss of glycosylation at S241 (P = 0.0231);
MVP		0.043
MPC		0.19
ClinPred		0.27	T
GERP RS		4.1
Varity_R		0.10
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs1764389392; hg19: chr6-42796792;