NM_198799.4:c.287A>T

Variant names:

• chr20-50841788-A-T
• rs755994429
• NM_198799.4:c.287A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198799.4(BCAS4):​c.287A>T​(p.His96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H96R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BCAS4 NM_198799.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 0 publications found

Genes affected

BCAS4 (HGNC:14367): (breast carcinoma amplified sequence 4) Predicted to be part of BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1247783).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198799.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS4	NM_198799.4	MANE Select	c.287A>T	p.His96Leu	missense	Exon 4 of 5	NP_942094.3	A0A804CEY2
	BCAS4	NM_017843.4		c.377A>T	p.His126Leu	missense	Exon 4 of 6	NP_060313.3	Q8TDM0-1
	BCAS4	NM_001010974.2		c.354+11408A>T		intron	N/A	NP_001010974.1	Q8TDM0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAS4	ENST00000371608.8	TSL:1 MANE Select	c.287A>T	p.His96Leu	missense	Exon 4 of 5	ENSP00000360669.3	A0A804CEY2
	BCAS4	ENST00000358791.9	TSL:1	c.377A>T	p.His126Leu	missense	Exon 4 of 6	ENSP00000351642.5	Q8TDM0-1
	BCAS4	ENST00000609336.5	TSL:1	c.287A>T	p.His96Leu	missense	Exon 4 of 6	ENSP00000477167.1	A0A0C4DGS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250888 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461662 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	1.6
DANN	Benign	0.47
DEOGEN2	Benign	0.069	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.033
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.059
Sift	Benign	0.35	T
Sift4G	Benign	0.12	T
Polyphen		0.40	B
Vest4		0.38
MutPred		0.45		Gain of ubiquitination at K122 (P = 0.1106)
MVP		0.14
MPC		0.70
ClinPred		0.22	T
GERP RS		-0.51
Varity_R		0.084
gMVP		0.58
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs755994429; hg19: chr20-49458325;