6-42828908-T-C

Variant names:

• chr6-42828908-T-C
• NM_001393499.1:c.575T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393499.1(BICRAL):​c.575T>C​(p.Val192Ala) 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. 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: 5.43

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
• BP4: Computational evidence support a benign effect (MetaRNN=0.34494442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BICRAL	NM_001393499.1	c.575T>C	p.Val192Ala	missense_variant	Exon 6 of 13	ENST00000314073.10	NP_001380428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BICRAL	ENST00000314073.10	c.575T>C	p.Val192Ala	missense_variant	Exon 6 of 13	1	NM_001393499.1	ENSP00000313933.4
BICRAL	ENST00000394168.1	c.575T>C	p.Val192Ala	missense_variant	Exon 5 of 12	1		ENSP00000377723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.575T>C (p.V192A) alteration is located in exon 5 (coding exon 4) of the GLTSCR1L gene. This alteration results from a T to C substitution at nucleotide position 575, causing the valine (V) at amino acid position 192 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T;T;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T;.;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.83	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	.;N;N
REVEL	Benign	0.092
Sift	Pathogenic	0.0	.;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.61	P;P;P
Vest4		0.61
MutPred		0.37		Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);
MVP		0.043
MPC		0.86
ClinPred		0.83	D
GERP RS		5.5
Varity_R		0.36
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: chr6-42796646;