17-61392121-C-T

Position:

• chr17-61392121-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2 BP4_Strong BP6_Moderate BS1

The ENST00000407086.8(BCAS3):​c.2738C>T​(p.Pro913Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000352 in 1,613,092 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (1 hom.)
• Consequence: BCAS3 ENST00000407086.8 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.71

Genes affected

BCAS3 (HGNC:14347): (BCAS3 microtubule associated cell migration factor) Enables several functions, including acetyltransferase activator activity; beta-tubulin binding activity; and histone acetyltransferase binding activity. Involved in cellular response to estrogen stimulus; positive regulation of catalytic activity; and positive regulation of transcription by RNA polymerase II. Located in nucleus; phagophore assembly site; and transcriptionally active chromatin. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.006275207).
• BP6: Variant 17-61392121-C-T is Benign according to our data. Variant chr17-61392121-C-T is described in ClinVar as [Benign]. Clinvar id is 3133332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000353 (516/1460810) while in subpopulation NFE AF= 0.0000891 (99/1111706). AF 95% confidence interval is 0.0000745. There are 1 homozygotes in gnomad4_exome. There are 270 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAS3	NM_017679.5	c.2738C>T	p.Pro913Leu	missense_variant	24/24	ENST00000407086.8	NP_060149.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAS3	ENST00000407086.8	c.2738C>T	p.Pro913Leu	missense_variant	24/24	1	NM_017679.5	ENSP00000385323	P3
	ENST00000585765.1	n.28+8095G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152164 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000640 AC: 159 AN: 248418 Hom.: 0 AF XY: 0.000667 AC XY: 90 AN XY: 134974

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000353 AC: 516 AN: 1460810 Hom.: 1 Cov.: 31 AF XY: 0.000372 AC XY: 270 AN XY: 726704

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000891

Gnomad4 OTH exome AF: 0.00118

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152282 Hom.: 0 Cov.: 31 AF XY: 0.000282 AC XY: 21 AN XY: 74460

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000639 Hom.: 0

Bravo AF: 0.000336

ESP6500AA AF: 0.000253 AC: 1

ESP6500EA AF: 0.000242 AC: 2

ExAC AF: 0.000447 AC: 54

EpiCase AF: 0.000491

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2022

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	.;T;.;.;T;.
Eigen	Benign	0.082
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.0063	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N;N;.;N;.;.
REVEL	Benign	0.056
Sift	Pathogenic	0.0	D;D;.;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.0050	B;B;D;B;.;.
Vest4		0.20
MVP		0.34
MPC		1.2
ClinPred		0.081	T
GERP RS		5.3
Varity_R		0.23
gMVP		0.45

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: rs200314899; hg19: chr17-59469482;