6-26448250-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006994.5(BTN3A3):c.718C>G(p.Pro240Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,613,262 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

BTN3A3
NM_006994.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

Variant links:

Genes affected

BTN3A3 (HGNC:1140): (butyrophilin subfamily 3 member A3) The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A3) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).[supplied by OMIM, Nov 2010]

BTN3A3 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14637351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BTN3A3	NM_006994.5 linkuse as main transcript	c.718C>G	p.Pro240Ala	missense_variant, splice_region_variant	6/11	ENST00000244519.7
BTN3A3	NM_197974.3 linkuse as main transcript	c.592C>G	p.Pro198Ala	missense_variant, splice_region_variant	6/10
BTN3A3	NM_001242803.2 linkuse as main transcript	c.308-478C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN3A3	ENST00000244519.7 linkuse as main transcript	c.718C>G	p.Pro240Ala	missense_variant, splice_region_variant	6/11	1	NM_006994.5	P1	O00478-1
	ENST00000707189.1 linkuse as main transcript	n.1000-104937C>G		intron_variant, non_coding_transcript_variant
	ENST00000707191.1 linkuse as main transcript	n.1001-84455C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

151676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

250964

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000254

AC:

371

AN:

1461468

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

174

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000184

AC:

AN:

151794

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000340

Hom.:

Bravo

AF:

0.000208

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.718C>G (p.P240A) alteration is located in exon 6 (coding exon 4) of the BTN3A3 gene. This alteration results from a C to G substitution at nucleotide position 718, causing the proline (P) at amino acid position 240 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

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.16

T;.;.

Eigen

Benign

0.070

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.81

T;T;D

M_CAP

Benign

0.0013

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

0.82

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.082

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.031

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.34

MVP

0.52

MPC

0.26

ClinPred

0.24

GERP RS

1.8

Varity_R

0.11

gMVP

0.021

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over